I'm guessing we're more likely to see graphical upgrades, bigger maps, and incrementally more RPG elements. MMO is a neat idea, but it's still quite niche on a console.
I wish they'd just let GTA as a franchise rest for awhile and use the basic design of the GTA games for other interesting situations. What if they made a game like GTA: San Andreas only encompassing the entire Gaza Strip and parts of Israel, and had you play as a Palestinian militant? Or a Taliban remnant in Afghanistan? Or hey, keep the crime thing, but make it more of a period piece, like maybe prohibition era Chicago / Detroit / Windsor? Imagine making liquor runs across the border.
The "safe" choice will be to just pick another city, make it more photorealistic, get more big names to do voice overs, and just give us "same thing, new story". It might even work, after all, the Final Fantasy games remain popular despite little effort to truly "reinvent" them.