Mikael: I don't think we are going to see a realistic, dying in the desert scenario. Like it or not, the name "Vegas " does bring some set responses to your average person: Neon Lights, Mafia (somewhat between "the godfather" and "sopranos" styles), Gambling, "People of Low Moral Fiber" and all that... Sure it would be nice if we had a dune'esque setting but I believe we are going to see a "New Reno" re-cook.
Personally i believe if they supported the New Reno with some story and plot backing, it can be made into an acceptable setting. Some oasis(es?) of life surrounded by the crumbling remains of the world (mock ups of Pyramids, Eiffel Tower and other landmarks)
I don't even demand a lot. Just leave some breadcrumbs that point to the existence of caravan networks, the bastard bad guy and his faction that controls the remains of the hoover dam (and the water for the region), the little BoS outpost that is trying to take over the said dam to gain access to the hidden old military bunker near the dam etc...
Whoa! I just created a weird first part main mission here
The main power of the region, as Ausir pointed out, would lie with the remains of the Hoover Dam and its water reserves. I would love to see a/the powerful bastard and his men controlling the place and demanding tribute and all from the survivor communities among the ruins. He could have his fingers at every business from chems to slavery to protection.
I would love to play the SOB that gains the backing of several unrelated communities (like a little crime family/clan, some gun nut rangers, a little BoS outpoıst and whatnot..) and takes down the bastard... only to find out that he has even bigger troubles to cope with