Continuity mistake: Whenever Megamind or Minion uses the disguise generator, their normal eye colour always show through their disguises, such as when they both disguise themselves as the Warden (the Warden has blue/gray eyes while Megamind has green and Minion has brown). However, during the final battle, Minion disguises himself as Megamind but he has Megamind's green eyes instead of his normal brown eyes.
Continuity mistake: While Megamind is in the Metroman Museum, he uses his dehydrator gun and turns Bernard into a little blue cube. He puts the cube in his pocket, then picks up Bernard's cellphone and glasses. At the end of the movie, inserted into the credits is a short scene where Minion is doing laundry. As he approaches the washing machine, Bernard pops out of it, having been rehydrated in the wash - with his glasses perched askew on his head.
Deliberate mistake: When Metro Man flies towards the observatory to save Roxanne, we see a typical "the-characters-see-what-the-audience-sees" shot - a Super-Man-esque shot of him with his arms stretched out in front of him with his fists clenched. This shot is then projected onto a monitor that Minion is watching. It would be impossible to achieve this. It's as if there's some sort of camera on top of the observatory filming Metro Man, which there isn't. We see the observatory enough times to see that there isn't, and even if there was, the angle at which it would need to be at would be impossible to achieve. The shot of Metro Man on the monitor is positioned right in front of him, panning backwards. A camera would need to be very long to achieve this kind of shot, but there simply isn't one present.
Continuity mistake: When Megamind parks his invisible car - just before he loses it - the car is parked significantly to the left of the "No You Can't" poster. Yet, when he finds the car again, it is directly in front of the poster.
Continuity mistake: At the beginning of the film where Metro Man is addressing Metro City, he asks them if they know what the greatest honour they have given him is. When he asks this he is standing at the edge of a pond. But once he tells them what it is, he is suddenly standing in the middle of the pond.
Continuity mistake: When Megamind and Minion are arguing about Roxxi, Minion extends his arm with the keys away from Megamind. Megamind presses a button that partially retracts his arm to a few feet long. When Megamind says, "Maybe I don't want to be the bad guy," Minion gasps and raises both hands to his chest. When he leaves to get his things and go, the arm is a few feet long and limp again.
Continuity mistake: In the final battle between Titan and Megamind, when Titan punches Megamind into the wall beside the invisible car, he hits him toasted his right. When he approaches him, he approaches from his left.