Wanted is a comic book which was, as Wikipedia so succinctly puts it, "loosely adapted" into a movie of the same name. Both are primarily action-focused, with relatively weak plots - so, really, the plot having been wildly changed between the two isn't that big of a deal.
There will be minor plot spoilers (with warnings) below; and fairly comprehensive plot spoilers in the plot section at the end.
The Comic
Wanted was written by Mark Millar, penciled and inked by J. G. Jones, and colored by Paul Mounts. The stock quote for Wanted, describing it as "the Watchmen for super-villains", is alleged to come from someone at the London Sunday Times. I say alleged, because I can't seem to dig up any first-hand evidence of this quote, nor the name of the writer. I can only hope that's because they're so ashamed of being utterly wrong that they've taken up sheep herding in some obscure and distant land. Not the part with the crook, the part where you run around and bark at the sheep, and then are mauled by wolves. Watchmen, after all, was actually pretty damn good.
Wanted isn't terrible. The art is good, the premise is interesting, and the action is good. The plot, however, fails to tie things together in any sort of interesting way, and the final package doesn't quite deliver. It's worth reading if you're bored, don't mind action without much depth, and don't have to pay for it. Otherwise, don't bother. Comparing that to something like Watchmen is, well, ridiculous.
Minor spoilers follow:
Wanted is a sort of dark, violent bildungsroman for the feckless main character, Wesley Gibson. Hauled away from a life he hates - from his job, to his girlfriend, to his best friend - by The Fox, he is informed that his supervillain father has been murdered. Wesley stands to inherit millions, provided he becomes a supervillain himself, and bodyguard to The Professor, a key figure in The Fraternity. Said group of supervillains has slaughtered or subverted every hero or superhero in their reality, and they essentially rule their world. The rest of the story follows Wesley's reactions and actions in regards to The Fraternity, its members, and his father's murder.
The Movie
Directed by Timur Bekmambetov, with James McAvoy as Wesley Gibson, Angelina Jolie as Fox, and Morgan Freeman as Sloan, Wanted was released in 2008. The movie is slick action, with an acceptable plot. If that sort of thing appeals to you, it's well worth watching. It's well put together, without ever really dragging, and the mostly excellent special effects (aside from one vehicular sequence) support keep the action entertaining.
The thing that most struck me on rewatching Wanted was how similar several large parts of the ending action was to Equilibrium - and how, despite the obviously higher budget and slicker effects, how inferior Wanted was in terms of choreography and overall impact of the action sequences. While I think that Ultraviolet proved that Kurt Wimmer shouldn't be allowed to make entire movies without adult supervision, his grasp and original presentation of action sequences is fantastic, and I'd love to see that combined with someone who can reliably make good movies.
Minor spoilers follow:
Wanted once again has Wesley being snatched from a life he loathes by Fox, this time with a no apparent strings inheritance of millions, and an introduction to The Fraternity, this time a group of assassins who follow the oracular interpretations of Sloan, vaguely equivalent to the comic's Professor, in taking out targets to make the world a happy place. Drawn back in not by force, but by his desire not to suck, Wesley begins training to hunt down his father's murderer, and the rest of the movie follows from there.
The Plots
Massive spoilers to follow!
The biggest differences between the two are the nature of The Fraternity and their stated purposes (and thus Wesley's nature and purpose, as he becomes one of them) and Wesley's father.
In the comic, The Fraternity is, by its very nature, an evil group. They've banded together to slaughter any force of good which could stand in their way, and now they slaughter innocents, steal, rape, and generally rampage their way across the globe. And, since this is comics, across several alternate globes as well. Wesley starts by killing random strangers, and works his way up to everyone who's ever pissed him off.
In the movie, The Fraternity is presented as a group for good, and this appears to have been historically true. However, Sloan has subverted the group for his own purposes - essentially, ruling the world, as in the comic. Wesley can only be convinced to kill anyone at all after Fox's personal revelation (no, not that one) convinces him that anyone selected by fate to die must really be evil.
Wesley's father in the comic has faked his own death in order to force Wesley to become "manly" and take control of his own life, while in the movie, Wesley's father is still alive, and has rebelled against the group upon finding it evil. Indeed, Wesley's movie father wants him to have the normal life that his comic book father wants to get him the hell out of.
Overall, the plot of the movie is fairly standard Hollywood fare, and for fairly obvious reasons (the protagonist shooting his former best friend's energy drink is OK in a movie; killing his former best friend because he feels like it is not.) While the changes are fundamental, and the premise of the comic is more interesting to me, the movie's actual execution is superior, and preferable.