This thread was merged with others, but I still stand by what was suggested earlier - a disabled protagonist, or at the very least a major secondary character.
I think people forget that "disabled" doesn't only mean "double above-the-knee amputee" or "wheelchair-bound". A blind or a deaf protag would be really, really cool. Or somebody who, either naturally or by accidents before the zombie apocalypse, was missing a limb. And there are lots of other disabilities, visible and invisible, that are viable options, too.
But I don't think it will be very likely, however awesome it might be to have positive images of disabled people in a difficult world.
Barring that, I agree with all of zgamer's ideas. I forget who posted it in another thread, but I also think it would be neat if there was a time jump to where Rick is now approximately in the comics, when people are more used to zombies.
Also... this idea will probably be shot when the game is out tomorrow, but Christa for season 2 protag?
