However, I'd love to see a Florida Fallout based around Cape Canaveral. Here's how I see it: Cape Canaveral still functions as the US's home to its space program. We know from Van Buren pages that space stations were intended to be in the FO universe. Canaveral was targeted heavily by Chinese nukes, but it also had strong defenses, allowing only partial destruction (like Mr. House saving Vegas for the most part). Being home to top scientists, on-site Vaults were created to protect America's best scientific minds. They survived fallout underground, with much of their technology and information with them. As generations passed, they educated their children to the best of their abilities, but they slowly became less adept over time - but still superior to scientists elsewhere. Eventually, the vaults open, and the inhabitants reclaim Canaveral and are trying to restore it to its original glory. They create a perimeter similar to the Boomer's in NV, and refuse admission to anyone else in the wastes. Eventually, using resources from their vaults, they manage to repair a significant amount of tech at Canaveral - Vertibirds, equivalents of the Liberty Laser for border protection, re-establishing connection to orbital assets (including weapons and communications platforms), and of course, one lone space shuttle capable of making only one or two trips. However, their numbers are small, so their influence in the wastes remains limited. Being completely self sufficient, no one goes in, no one goes out. People living in the wastes are constantly trying to get in, having little infrastructure. Outside of Canaveral would represent something more along the lines of the Capital Wasteland instead of the Mojave.
The Enclave should appear as well, serving as a small cameo appearance. Since they are remnants of the US government, it would stand to reason that they would have small outposts all throughout North America. Canaveral just makes sense for one. The PC can run into a small, hidden bunker manned by only a few Enclave personnel. They are monitoring the restoration of Canaveral with great interest. Upon taking the base, the PC could tap into the outpost's databanks and learn about the overall location of all Enclave bases.
You could also throw in a cool little scenario with advanced communications. Canaveral could contact all the known major players - BoS, Enclave, NCR, Legion, West Coast BoS, Vegas, The Institute, Ronto, The Pitt, and so fourth. I'm sure something cool could come of it. These factions could vie for Canaveral's alliance, and the player could choose to nuke say..... Shady Sands, Vegas, or the Citadel. It would also be interesting to use orbital installations to view the condition of the rest of the world.
DLCs would take you to a functioning space station were you get to nuke some foreign threats to North America, and a Canaveral expedition could be sent to Cuba to investigate Communist bases and missile silos existing there before the war began.