Rocks fall, everybody dies. It would all be Homer's fault, but nobody would care.
Because they'd be dead.
More realistically, it'd probably just be like any other episode. I think I remember Groening saying at some point that he didn't want to make a "final" episode, so we'd probably end up with something as awful as the Lady Gaga episode as the series finale.
Ideally, I'd like them to actually make it as good as The Simpsons was at its peak, but that's probably expecting too much.