The games have often been about a city or such. Commonly, there is only 1-2 big cities in GTA's.
What I was thinking...
There should be an area as big, or perhaps bigger than GTA V San Andreas. No, wait, you'll hear my "idea" now: There should be one big city and some other environment. But as the idea, there should be a big partially destroyed city somewhere for finding exciting things and such.
Even the story could connect to it, like if the game opens with a Weazel News broadcast about "<city name here> gotten partially destroyed due to an earthquake/tsunami/alien invasion/other natural disaster". The main character (1 or more, it doesn't matter) would have lost his house and all other possessions in the event, and thus (s)he has to result to committing series of crimes in order to keep the high-end life (s)he used to have.
I have heard/seen a lot of people talk about the same pattern GTA follows (commit crimes -> get money -> live well). This idea would be have difference to GTA-franchise by having a destroyed, abandoned city to explore and have a story-wise connection to while you could still do all the things you've used to do in past GTA's (driving, shooting, RPG-rampage).
I guess the game would take a serious tone with the idea, but that's just my thought.