We are really breaking some new ground here.
Bethesda, with TES, has always gone by the idea that everything happened though it may not have been the player that accomplished a paticular deed. However, outside Daggerfall (which they worked around) their games have very few choices that truly change the nature of the story. You always stop Dagoth Ur. Dagon is always stopped by Martin's sacrifice. Alduin is always defeated in Sovngarde. On a lesser scale, Almalexia is always killed, the Divine Crusader always collects the Relics and stops Umaril, and Harkon is always defeated.
Thing is... Fallout is different, and has been since before Beth got hold of it. Devs make 'canon' choices for the future timeline. I'm wondering how Bethesda are going to handle it.
Returning to Vault 101, you can either fix things and leave them inside, screw things up and leave them inside, kill everyone inside, or even force them out into the wasteland where they will be picked off in random encounters.
Tenpenny Tower is either healthy and hale, or a refuge for murdurous Ghouls.
The Brotherhood is either the healthiest it has ever been, controlling the spic... er, water, and growing, while making actual headway against the mutants. Or they are a ruined minority of bitter soldiers roaming downtown DC, their Citadel destroyed by an orbital strike.
Harold is either slowly spreading lush plantlife across the wasteland, or a burned husk surrounded by mourning followers.
Since not everyone bought Broken Steel, it's even concievable that the Lone Wanderer died, too.
A good portion of the games important NPCs can die at certain points in the game, which in TES would mean we will never see them again. Exceptions that spring to mind are Doctor Li and... well, Doctor Li.
How do you think Bethesd are going to going to handle it? See, i'd say good karma choices for all, but this is Fallout and a few bad or neutral karma choices might make the setting more interesting going forwards. We know the survival guide was completed, from NV, but the game was (understandably, given the geographic distance) vague of details.
Thoughts? I think it might be interesting to ponder, as I expect FO4 to at least be announced this year, even if its two or more from actual release.