Best rumour i've heard (actually from a few months back and starting to be respread) is that there will be multiple characters you control rather than just one character.
So the first chapter is character one. chapter 2 etc......ten hours or so as each characters, all with there own storyline that ties into the larger overall plot. I think i'd prefer that.
That would certainly be interesting, though there would be a danger of becoming "detached" from the characters. Also, the whole point of GTA is the whole "rag to riches" thing. I think that achieving this with multiple characters is a big ask.
I would like to see more of the RPG-esq elements from San Andreas return. From buying houses, changing your outfits and hairstyles, and making yourself fat. They're only little details, but add a bit more individuality to the game.
Perhaps a slightly branching story would also be cool. GTA IV kinda did it with the last mission, but they could build on it.