Metro Man: We all know how this ends: with you behind bars!
Megamind: Oooh, I'm shaking in my custom baby seal leather boots!
When Megamind as Bernard is in the library with Roxanne, the book he is reading ("Megamind Unmasked") has a description on the back of a self-help book entitled "The Happiest Me I Can Be". This is the same book that Metroman read (shown later in flashback) that caused him to decide to cease to be a hero. See more...
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Continuity: 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: 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: 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 thing and go, the arm is a few feet long and limp again.