The problem with this show going long is if they don't milk the Enclave stuff and don't get into Aliens then they have to invent new lore and we all know how that worked for Game of Thrones.
There isn't much of a risk of running out of lore/factions. I doubt we're going to get some 10+ season thing like Walking Dead. Besides, Bethesda isn't going to let them perma kill any given faction
