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Okay, so... it's kind of like a play on the familiar Superman mythology, but with the villain as the protagonist. It starts with two babies from different worlds coincidentally being sent off in little spaceships to live on another planet (Earth). Much like Kal-El of Krypton, the baby who would grow up to be the supervillain Megamind was sent away by his parents because their planet was on the brink of destruction. (The backstory for the baby who would grow up to be the superhero Metro Man isn't revealed, but presumably it's the same kind of thing.) But, while Metro Man (Brad Pitt) winds up being raised by a wealthy family, Megamind (Will Ferrell) winds up in a prison, being raised by the prisoners. (There's also a talking fish named Minion, voiced by David Cross, whom his parents sent along with him to Earth, who ends up being Megamind's evil minion, naturally.) Anyway, we see a bit of the childhoods of Megamind and Metro Man, and how a rivalry developed between them, but most of the movie is set when they're grown up, after they've been doing the whole hero/villain thing for some time. And the routine has grown rather stale. Megamind kidnaps Metro Man's girlfriend, reporter Roxanne Ritchi (Tina Fey). He unveils his latest plot to destroy Metro Man. And much to absolutely everyone's surprise- including Megamind's- this time it actually works. Metro Man is killed, and Megamind takes over Metro City (which he always pronounces as one word, "Metrocity").
But, eventually Megamind gets tired of running rampant with no one trying to stop him anymore. So he uses Metro Man's DNA to create a serum which would give someone the hero's super powers, so he'd have a new nemesis. The serum ends up being shot into Hal Stewart, Roxanne's cameraman. Megamind uses his holographic cloaking watch to disguise himself as an alien who he tells Hal is his father, and begins training him to be a hero (who he calls "Titan"), to eventually fight Megamind. Meanwhile, Megamind also uses his watch to disguise himself as Bernard, the curator of a museum, and begins seeing Roxanne socially. At first they want to work together to figure out a way to defeat Megamind, though the relationship develops beyond that (until she learns that Bernard is really Megamind). Unfortunately, Hal/Titan had always had a crush on Roxanne, and thought now that he had super powers, she should want to be with him. When he finds out she's seeing "Bernard," well... it throws a major monkey wrench into Megamind's plans.
I don't really want to say any more, but there are some twists, which were perhaps somewhat predictable, but still cool. I won't spoil it any of it, anyway. Um... the movie actually plays on lots of genre tropes, and turns them on their heads, for the most part. And it can be reminiscent of various other (better) animated movies, but I still found it fairly unique, I guess. Anyway, it was pretty funny, and I've always liked supervillains, especially quirky ones, and... the ultimate moral of the story may have been done to death, but I still thought it was done well here. There were some genuinely clever bits (including the fact that baby Megamind never actually heard what his father told him about his destiny). And the cast was really good. And I guess that's all I can think to say. It was just a pretty fun movie.