That classic http://tvtropes.org/pmwiki/pmwiki.php/Main/AmnesiacDissonance formula would SO be perfect for the Fallout universe, like they were made for each other.
Not knowing anything about the Wasteland or the War or anything, or even who you are, maybe "waking up" all alone in an long-abandoned Vault, and having to piece everything together on your own, maybe just outside the borders of the United Stat- HEY, how about Hawaii??! :drool: to really capitalize on that factor of exploring-the-Unknown.
Oh sweet jeebus yes, Hawaii would be so perfect for the next, post-NV game: an America outside America, to bring something really fresh into the show, not to mention the added elements of an aquatic environment between the islands - maybe there could even be an artificial island, made of metal, predating the War or maybe built later out of the wreckage of hundreds of ships. Anyway it should be something as exotic as the city of http://en.wikipedia.org/wiki/Sigil_(Dungeons_%26_Dragons) as far as FO's theme and contemporary physics will permit.
and you could explore all that by playing the part of someone without any memories of their past self, and possibly with hidden powers - maybe the result of some FEV experiments?
So, discuss! Let's go nuts building the next-next FO while we wait for more details on NV to come up ^_^ The Main Hook should be a Nameless-One or Revan-like Player Character.
and as an offshoot, a thread to discuss the prospect of a http://www.gamesas.com/bgsforums/index.php?showtopic=1075935 in any case.