Now, this is going to be the thermonuclear bomb of all video game/politics/moral warrior outrage...but I'd like to see a Fallout game done in the deep South. Practically anywhere along the Gulf would be awesome, but I'm eyeballing Houston, New Orleans, or the Everglades as prime candidates. Heck, with a New Orleans setting in Skyrim's engine you could make the game's map the Mississippi delta and a good chunk upriver. Just imagine what the guys responsible for the flora and fauna in Morrowind could do in a nuclear post-apocalyptic game set in the Everglades.
It would be a great idea to completely take the piss on FO2/NV standbys, by having a New Confederacy that embraces slavery and antebellum culture juxtaposed with retro-futurist aesthetics, tribals and "raiders" who make up an underground railroad and embrace technology in the absence of the BoS, mutant rednecks a la Point Lookout, and even some hilariously-mutated animals...mutant opossum or armadillo, anyone?
Heck, even deconstruct the typical FO origins and such. The southern Vault Dwellers were the ones who built the New Confederacy, and the PC is a slave who escapes somehow. That could let the player select race opposed to being forced to play human.
Either way, I don't really care as long as they add vehicles and vehicular combat. Heh.