The destruction of the Staff of Chaos, the Dragon Breaks and Warps in the West, the sundering and separation of the Heart of Lorhkan from Nirn, the negation of the pact between Akatosh and the Empire (and also the possible banishment of Akatosh as a part of the tri-soul Alduin/Akatosh/Auri-El)
Skyrim is also to be the last Elder Scrolls Game of this console generation.
I'm thinking that Alduin will succeed in destroying and remaking the world. The Next Elder Scrolls game could be a complete departure from what we know. Tamriel, Akivir, Atmora, and Yokuda may not exists anymore. Races could be wiped out, drastically changed, or new ones could spring up. A huge leap in time to a more advanced (industrial revolution) time, or a step back into something similar to the Merethic era could take place.
I'm sure TES games will always be sand-box rpgs, but the lore and things that are familiar to us could be different when we pick up TES:VI in 10 or so years.