In Fallout 3 you are given the option to destroy Megaton with a nuke...at the end of brokensteel, you could destroy the citadel, and yo can help ghouls kill everyone in tennpeny tower. All of these options involve dramatically changing an area or region and removing any quests for that area. so, i agree with the others that it could be nuke time for someone in the mojave. Another idea is that, maybe, you will get ulysses as a follower. I believe someone said that all of his companion codding is still in the game files....sooooo
As much as I'd love a shiny new companion, it did say that it would affect part of the wasteland. And yes, Beth has blown stuff up in the past, but I still doubt that they will destroy settlements, especially if they have to record dialogue for all of the people who will inevitably be talking about how Novac or whatever was just nuked.