Having not read the entire thread, I'm not sure just how many of these cities have been debated to death, but I do have a few ideas...
New York City - This would probably be the easiest of the locations to set up a story in, although a difficult one to make work technically. It's an opportunity to create a very claustrophobic atmosphere, with skyscrapers and all manner of other buildings towering above the player, and dark, winding subway tunnels that have cracked and allowed mutated (possibly sentient?) vegitation to take root in the tunnels and expand. There are plenty of songs about New York to fill out a soundtrack, and there are TONS of cultural groups, even from the days before globalization (Irish, Poles, Italians, etc.). New York has been its own little world for well over a century, and would undoubtedly be so in the wake of a nuclear event.
You have ample DLC options with New York, particularly the Commonwealth to the north and its associated Institute, referenced in FO3, as well as New Jersey or eastern Pennsylvania to the South. DLC could serve as a counter to the claustrophobia of New York, providing open, hilly savannahs and pastures There are also a number of distinctive landmarks; not just Staten Island, but the Empire State Building, the Chrysler Building, the New York Public Library, Madison Square Garden and Yankee Stadium (though those image rights might cost some serious coin). The trick is to produce enough variety or create enough atmosphere to make audiences overlook the fact that everything is gray and brown.
Detroit - When mulling this one, you have to bear in mind that the withering wasteland we know as Detroit to day was quite different in the first half of the 20th century. It was a booming automotive town and industrial center, and people flocked to the city looking for work. Ronto could be worked in as DLC.
Chicago - Like New York, there's lots of culture to be had here, and like New York, I think it will continue to be tossed around as an option until it is used. We've only seen very little of Chicago or the Midwest in general, and this would be a great place to fix that. You've also got the Willis Tower to explore; maybe it's the Enclave's Chicago outpost that was talked about in FNV?
Miami - Miami is my personal favorite choice. It's a city that has always had its own aesthetic. There are lots of bright colors and exotic activities, and everything is tinged with a Latin flair (something they could reflect in the soundtrack, maybe with a little Cuban jazz or big band, like Perez Prado). It's a lush, colorful, and vibrant city in the tropical sun of Florida, much different from the Mediterranian sun of California. It'd definitely be interesting to see how the city changed in the wake of a nuclear holocaust. Also, the Everglades are nearby. Three words: Giant. Mutated. Alligators.
Nashville - In the mid 1950s, Nashville began its rise to prominence in the music industry as country really took off, with one foot in rockabilly and another in bluegrass. It's the epicenter of the cultural South, a place we have seen absolutely none of. Is the Confederacy making a comeback? Maybe there's a monarchy using the Parthenon as its royal palace? It's also a great opportunity to make technology very, very scarce, as many portions of the South were just becoming modernized in the 50s and may have stayed that way to some degree for the last century of America's pre-War existence.
Extension of the Core Region: Pacific Northwest, Colorado, or Texas - All of these regions could offer something new while keeping the Core Region's familiar names and cultures in the game. In the Northwest, there's the question of how the dense forests survived the War, if they're regrowing, and how the technological Mecca that is Seattle has held up over time. We've heard lots about tribals in these parts, as well, and I'm always interested in what tribals are up to. Maybe they revere the technology and are fighting against the Brotherhood of Steel to protect it?
Colorado could pick up a concept with the Van Buren script, with the player starting out as a frontier scout for NCR, something goes wrong, and you're cut off, with the vast emptiness of Colorado all around you.
Texas has always been thought of as its own country. Well, who's to say it isn't three or four? Texas is such a massive piece of land, that in a world where communication is spotty at best, smaller nations arise and vie for territory. Texas could essentially be Europe In A Box.
I'm eager to see what they do with it, and I'm going to try to keep an open mind if they make a choice I don't initially care for. I'd just like to see more of America than what has already been established. NCR is politically stable having survived Tandi's resignation and death. The Enclave is gone, and the BoS is ultimately not a threat. Don't just totally give up that part of the universe, but at least let it take us to a few different places.
