In the first Prototype game, protagonist Alex Mercer was the good guy. In the second game, he's the bad guy.
In this latest trailer, the game's developers waxed about Mercer and the decision to make him the enemy. The thrust in the sequel is that players are James Heller, who was infected by the "Blacklight" virus, and are out to kill Mercer, the man who infected Heller.
Be sure to sit through the talking heads - there's some cool gameplay footage towards the end. Or better yet, skip ahead.