Originally, my thinking was a "modern", NES with structured rules, starting in 2177, with created factions. However, there are a myriad of problems with that idea, starting out with the most obvious: What to do with the rest of the world? Areas outside of America are very rarely talked about in Fallout, and are never fleshed out. Thus, a fresh start in 2161 at the time of the first game would allow nearly 100% freedom for players to create their own factions, and completely define the "NESified", Fallout universe at the start of the first game in the original Fallout canon.
Doing so, would leave me with the belief that to best structure this form, the NES would be story-based a la Back to Our Roots. Out of all the people who seem interested, everyone seems to favor a story-based Fallout, from what I've seen. Be this true?
EDIT: Even so, I want players for the Brotherhood of Steel and the Enclave, if only because those factions are so necessary and were established respectively hours before the lights went out, and years.