I highly doubt that Skyrim will be the last Elder Scrolls game. Oblivion had a plot that could easily have been the end of everything, but it wasn't.
Hell, Morrowind's story threatened all existence, as well, but we've got two games after it.
Not to mention, it's just simply too profitable.
I wouldn't mind playing in one of the previous eras, but that would be pretty hard on Bethesda's part considering anything the player does, unless it's completely insignificant would entail a
major retcon. I'm talking bigger than Cyrodiil being medieval France kind of big.