During Bethesda's E3 Showcase, game director Todd Howard offhandedly mentioned that West Virginia is the perfect setting for a Fallout game because it's where actual nuclear secrets are kept. If you do a little digging into the history behind the featured locations they've unveiled so far, you'll quickly see that he's telling the truth.
Just like in the game, one of America's most secure nuclear fallout shelters is located outside of White Sulphur Springs, West Virginia. It's called The Greenbrier Resort.
First built in 1858 as a resort for Northerners and Southerners alike, it was re-purposed in WWII as a relocation center for Axis diplomats before being retooled again during the Cold War to become a nuclear fallout shelter for diplomats nearby in Washington D.C.
As part of a project code named " Greek Island," Greenbrier was modified to be able to support every member of congress and their families beneath two feet of reinforced concrete. The bunker was kept secret throughout the Cold War before being finally revealed in a 1992 Washington Post article.
The most interesting tidbit of West-Virginian nuclear history is that Morgantown, the third most populous city in West Virginia, was also home to part of the P-9 Project, an essential piece of the larger Manhattan Project. Although the construction of the nuclear bomb took place all over the United States in secret, it was in Morgantown that progress was made in developing "heavy water."
Heavy water, or water that contains higher amounts of the stable hydrogen isotope deuterium, is needed to modulate nuclear reactors. It's no coincidence that Morgantown became home to the Morgantown Ordnance Works, an ammunition manufacturing facility responsible for (among other things) producing much of the TNT used during World War II.
A second ordnance works located nearby in Point Pleasant called the West Virginia Ordnance Works also seems like it'll be interesting to see in-game. The presence of it's explosive secrets with the volatility of massive-scale arms production combined to form the basis of local myths that state a mutated Mothman lives nearby — which you can be damned sure will make an appearance in Fallout 76.
But these tidbits of nuclear history just scratch the surface. Parts of Operation Plowshare, in which the U.S. government was testing the use of nuclear weapons in mining operations, was also conducted in the West Virginian counties of Logan and Boone.This, and all of the other nuclear blasts that would have occurred in-game, may also help reshape the map (since the obviously Point Pleasant is closer to the smaller but real-world Mason, WV.) Even the above map hints at where rivers may have once been.
The mountains in West Virginia are also home to the seventh largest uranium deposit, which you'll likely be able to explore on your post-apocalyptic romp. Pretty much everything you need to create a nuclear bomb is right there in West Virginia — and it'll be up to you to explore it all.