Bruce Banner/ The Hulk - Johnny Galeki (Leonard from Big Bang Theory). Johnny plays a nerd really well. The casting of the Bruce Banner has always been cast as normal science guys, they are Super Heroes without the SUPER before they even become the hulk. Why not cast him as the weird science guy that is a nerd in every sense of the word. The other possibility would be to cast Jim Parsons or Simon Helberg.
Cast Zooey Deschanel as Betty Ross, the female lead. I don't think it should be a comedy but when you look at scientists and geniuses not all of the are straight laced and boring like the people that have been cast in the past. Mark Ruffalo seems to have been the best from the past that I have seen as he seems has a sense of humor in the movies.