NOTE: It's been a while but finally another great spoiler sent in by Brentage5000.
The movie begins with our main Igor (John Cusack) telling us a little about his home, Malaria. Once upon a time it was a beautiful sunny place, but then the dark times -- literally, with dark clouds covering the whole land -- came, and evil King Malbert (Jay Leno) came up with a brilliant idea -- turn evil. Basically, making being a mad scientist a legitimate occupation by holding an annual contest whereupon the strongest, most deadly invention would be released upon the world unless an exorbitant fee is paid. Everyone got behind it, but in order to do it right the need for Igors -- hunchbacked assistants -- grew....people whose main goal is to pull the switch when told. We see a couple of them in action, and then we meet our Igor, who thinks he is much better looking than those other guys. His "doctor" is Dr. Glickenstein (John Cleese), who we see at the penultimate moment yelling "Pull the switch!" Unfortunately, Igor is busy in his room, drawing down ideas for inventions, his real passion. He hears the doctor and hurries into position, making excuses, but it doesn't matter since the whole thing comes crashing down. Glick tells Igor to run out and get a 16-watt transistor, although Igor suggests a 21-watt might be better. Glick rages at Igor but is calmed by his foreign girlfriend Heidi, who Igor secretly loves, and storms out, at which point Igor's friends -- or inventions -- show up. One is a weasel that can survive anything named Scamper (Steve Buscemi), and the other is a brain in a jar on wheels with a retractable winch for an arm named Brain (Sean Hayes). They come out and mess around the lab. During this, we also learn about the other top scientist in Malaria, Dr. Schadenfreude (Eddie Izzard), who gets no respect from the king despite having won the last seventeen fairs. He rages about this injustice near nightly to his girlfriend Jaclyn (Jennifer Coolidge) on a near nightly basis, and these arguments usually end with each of them slapping Dr. S.'s Igor (Christian Slater, who will hereby be reffered to as SI when necessary) silly until he collapses, at which point they make out.
Anyway, back in Igor's castle, Igor returns with two transistors, a 21-watt one which gets thrown at his head, and a 16-watt one which gets installed in the machine. He tells a reluctant Igor to do that thing and Igor sighs and pulls it. Electricity sparks all over the covered shape and Glick starts cackling and yanks the tarp off, revealing a massive rocket. Before he can properly ride in it and celebrate though, the rocket explodes, taking him with it and leaving only his robotic right arm. Igor panics at the sight, although Scamper's only response is weak enthusiasm that they can now get rid of that ugly rug in the front hallway. Within moments, though, the trio hear a knock at the door and find Malbert there. He demands an explanation and a desperate Igor says that Glick has created life, which causes a hidden Brain and Scamper to hang their head parts in frustration. Malbert buys it though and heads out, and Igor takes Brain and Scamper to his room, where he shows them his plans to build a giant killing machine. They throw it together over the next day with mismatched parts (example = one arm is normal, and the other looks like it was cribbed from The Incredible Hulk somehow), but since the thing is about fifteen feet tall, that's a minor issue. With five days remaining before the fair, Igor excitedly inserts the essential Evil Bone into the monster's thumb, screws the thumb down, yells, "PULL THE SWITCH!!!" and.....nothing happens. Scamper glares at him saying, "Do not yell at me," and eventually Igor remembers his manners and says please, but then Brain wants to do it, but Scamper beats him to it, the switch is pulled, lightning comes in, and.....nothing happens. Igor turns away in defeat with Brain following, telling them to get rid of that thing, and Scamper says that that won't be a problem, Igor turns and sees....nothing. They wonder what happened to the body, and Scamper says, "Maybe that's because she's RIGHT BEHIND YOU!!!" Igor and Brain scream and turn and see...more nothing. Brain shrugs and says it was just a thought. Suddenly they see it right behind Scamper, just before it runs through the wall, escaping them and forcing them to give chase.
Meanwhile, Dr. S. and Jaclyn are picking their way over to Igor's castle with the intent of stealing Glick's plans for whatever he'll be bringing to the fair. When they arrive, however, they find three things -- Glick's arm, the exploded rocket, and Igor's blueprints. He realizes Igor's plan to be seen as more than an Igor, and decides to stop him and claim the monster for his own. Meanwhile the boys have tracked the monster to a home for blind orphans. Hearing the screaming inside, they realize the monster must be doing some unspeakably evil thing to the orphans, which...you know....is great, but still...orphans...well, anyway, they bust in and see....the monster twirling the cute little orphans around like on a carnival ride individually before gently setting one down and picking up the next one. Igor enters, confused at this display of....not-evil, and the lady who runs the place (who may or may not also be blind) says what a delightful time the kids are having. Igor tries to get the monster to come with him, but instead she just picks up a paper flower the kids made, which the manager charges him for. Sighing, he buys the lot and uses them to make a trail leading back to the castle. Once there, he theorizes to Scamper and Brain that one evil act should be enough to activate the evil bone in her. Scamper comments that she wouldn't even hurt a fly....and sure enough, Igor is soon ordering her to smash that little buzzer to kingdom come. She roars, brings her hand down on the table, walks past an ecstatic Igor to the door....and then releases the fly into the cool night air where it flits about happily. Igor loses it and starts railing against the monster, telling her that she's supposed to be evil, but she mispronounces that as Eva and starts thinking that's her name. Igor sighs and decides there's only one thing to do.....get her brainwashed.
Some time later, they all arrive at Buzz Offman's Brain Wash, run by The Fly and his counterpart. Igor sets her up with an Axe-Murder Massacre special and while she's being done he treats himself to the massage chair as Brain gets a wash and wax and Scamper examines some get ill cards, including a Wish You Were There that transports you to your enemy's lair and a Mothers Day card that blows your head up, which after opening and suffering from he gives his seal of approval. Meanwhile, we check in on Brain, who is trying to change the channel on his pods TV and having no luck. He ducks out a second and goes into Eva's pod to grab her remote, but it's not working either. However, it does manage to change the channel in Eva's pod from a collection of grisly murder scenes to an episode of "Inside The Actor's Studio". One hour later, both pods finish their cycle. Brain exits with a tip for the assistant who gave him his shine. The trio waits for Eva to emerge. The door slides open, and Eva exits with a roar. The guys scream, and suddenly she's asking if that was too much and apologizing for possibly offending them. It soon becomes apparent that Eva (Molly Shannon) did not go through the right procedure, but because of the lifetime guarantee, they're stuck. They head back home with Eva being worried about paparazzi for some reason. Suddenly Dr. S. shows up with SI, Jaclyn, and a shrink ray trying to eliminate the competition. After jumping a canyon and narrowly avoiding some shots from the ray, one shot goes by and starts shrinking an arch that they need to pass through to get home. Brain screams that they'll all die except for Scamper, since he's indestructible. This makes Igor remember that he made Eva's skin indestructible, and he gets her to raise her hand by asking who wants to be a famous actress just as Dr. S. fires at them, making the shot ricochet and hits Dr. S.'s group, shrinking them instead. Unfortunately, Igor's car ends up going off a cliff, but Eva is strong enough to save them all just in time. However, Brain takes the opportunity to gloat that he really saved them by switching the channels to the actor thing, making her still good, instead of leaving it where it was and possibly causing her to either let them fall or kill them herself, which makes Igor go crazy until he gets the idea to use this acting desire by making Eva think that she's auditioning for a role in an updated version of Annie where Annie is in a huge fight with other characters ("How avant-garde", says Eva).
The next couple days go by fairly quickly, with Igor trying to direct Eva in preparation for her role, with her greatest contribution being the idea to spin around at the end, which inadvertently wrecks the whole set throwing things everywhere, which Igor realizes would be a great finish to the fight, so he keeps it in. The rehearsals are going so well, in fact, that even the normally sour Scamper is getting into his job of fashion designer, despite Brain's constant (and possibly purposeful) mutilations of him. At the same time, Dr. S. - restored to normal size somehow -- is watching interviews between the King and invisible TV personality Carl Cristall (Arsenio Hall), host of Cristall 'N Clear discussing Dr. S's chances of success and Carl's dislike of pants. He and Jaclyn get into another argument, but the slapping is sidestepped when SI rolls his eyes, slaps himself twice on each side, and collapses, leaving nothing but the kissing for the others. Back in the castle, Eva has called the boys together to give them some pre-audition gifts -- a beret for director Igor, a nametag that actually says Brain instead of the Brian scribbled on Brain's jar for Brain, and pictures of Igor and Eva and Brain for Scamper, so he'll never be alone when they're gone. Scamper reminds Igor to "get" Eva's "gift", and Igor runs into the other room and returns with a locket that was left lying around. She loves it and runs off, overcome. Igor goes out on the balcony for some alone time, but at that point, Heidi shows up with a card for Igor from someone. He opens the "Wish You Were There" card and is immediately transported to.....a sauna at Dr. S.'s estate. Eva shows up back at the castle, but Heidi somehow just freaks and calls her ugly.....which soon has a determined Scamper making her look better than ever before. Back with Igor, he is being wined and dined by Dr. S. about letting him have Eva, but Igor refuses, even when Dr. S. reveals that he knows that Glick is dead. Igor panics and runs out, heading back to the castle. After he leaves, Dr. S. and SI are let out by Heidi, who turns out to be Jaclyn in disguise. Igor arrives home just as Eva is coming down the stairs all glammed up. She starts towards him....and trips in the high heels, crashing into him. Before they can start talking, Igor is lured out back by "Heidi". After he goes, Dr. S. steps out of the shadows and they set things up to make it look like Igor is passionately making out with Heidi. Eva leaves with Dr. S. just as Igor breaks free and runs back into the mansion to find the cops and king waiting for him....seems somebody tipped them off that Glick was dead. They throw Igor into an Igor recycling pit, not believing his story, and leave, not noticing Brain and Scamper breaking into the pit and going after Igor.
All this is taking place just hours before the fair is scheduled to begin. Over in the locker rooms, Dr. S. is trying to get Eva, who is wearing a red Annie dress and wig because she still thinks its an audition, eviled up and finally manages to activate her evilness by calling her ugly, turning her into a Terminator-like goliath. Meanwhile, Scamper and Brain have caught up with Igor and managed to end up chained right alongside him waiting to go into the incinerator that "recycles" all unwanted Igors into whatever. Brain tries to shout some sense into Igor and succeeds just as the machinery comes to a stop. Brain and Igor look at the controls and see a footless Scamper standing there, having chewed his legs off to get free. As soon as they grow back, the trio escapes via a secret staircase they find and realize that their just below the weather beacon and directly above the arena where the fair is being held. Igor looks up and, following a hunch, continues to follow the stairs to the very top, above the clouds. There he sees that the weather beacon is actually pulling all the clouds towards it, meaning that Malbert created the darkness as a means of kick-starting the evil economy. Igor heads back down and takes a rope to drop into the arena while Scamper and Brain try to deactivate the beacon. Down below, the fight has begun, and Eva is doing remarkably well, taking the choreography from the rehearsals and beating down all competitors while singing "Tomorrow" at the top of her lungs. At the same time, Dr. S. sneaks up on Malbert and usurps the throne from him, which was his real goal all along. Just at that moment, Igor drops in and is confronted by the angry Eva. He starts trying to calm her down, saying that she was right all along and that everyone has an evil bone in their body, but people only choose to activate it. He manages to get through to her just as Scamper decides to chew through the control wires, making sunlight shine directly onto the mismatched couple. The light soon floods the stadium, and Igor takes the opportunity to tell the truth about what Malbert had been up to, making the whole population rise up against him. Watching from the king's booth, Dr. S. realizes he's done in this town and runs just as Jaclyn realizes she's out of pills and reverts back to her normal, Igor-like shape.
One year later, we see King Igor entering the stadium for that year's festival. He is confronted by Carl outside over the pants issue, but manages to sidestep him and the question and get inside. He goes to Eva's booth, where we see that instead of an evil celebration the fair is now an arts celebration. As Scamper works on the outfits of the blind orphans from earlier in the film and Brain tries to create his own act, Igor pulls Eva aside and shows her some plans he's made for something. She asks if he really thinks they're ready for that, and he says that if it doesn't work, than they can just adopt, and we see that the plans are for a dog built in the same fashion as Eva herself was. A fanfare plays outside, and the carnival begins as hundreds of balloons are released into the bright and cloudless sky.