The amount of variety is pretty high, there's no reason you can't play it over and over. You've got different investigators, different decks, varying maps, varying act or agenda cards, varying encounter deck order, and varying draws from the bag. Each game should have plenty of room to turn out quite different from last time.
I'm more worried I won't be able to keep up with the vast ocean of content. Oh look, a new deluxe box came out. Now I've got to run five more new guys through my old campaigns PLUS run my old investigators through the new scenarios. There won't be enough hours in the day to consume all the replayable content this game will have.