In the next GTA I'd really like to see the protagonist have more of a personal motive for more missions than in IV. So in other words, a plot that is driven more by the character's personal stake in the situations as opposed to doing everything simply for money. GTA IV was a step in the right direction but you were still very much the middle man with little say when it came down to it.I understand it can be hard to incorporate that into a lot of the missions but if it was possible to make it more propminent throughtout and it would always be a large theme of the game. Niko's search for 'someone' took a backseat throughout pretty much only to crop up every so often.
I'd very much like to see a return to the more rurual side of SA. It this was to be included then wildlife is essential. I think that's a strong possibility since RDR is including wildlife on the same engine so they're already a step there and they did use some RDR wildlife footage in one of the BOGT news videos I believe!
Obvious expansions such as more weapons, cars, side missions/activities.
But I believe that a more personal approach to the story would be the biggest step up for me.