It is very possible, and Blizzard has already talked about this, that the game is going to have 2 expansions. They have also said that D3 is the end of the franchise. As far as I see the lore (careful, may contain spoilers) we can all distinguish clearly two possible ways of writing these two sequels:
1- Focusing in the hunting down of the five Sins, i.e. Azmodan's Lieutenants; the ones that are not supposed to appear in D3. Place: Hell/Sanctuary.
2- Focusing in discovering what happened with Malthael, any remaining angels, and the final destiny of the World Stone. Place: Sanctuary/Pandemonium Fortress.
Both of them make perfect sense to me with the information that we now have. Both of them will be strong games that I am sure will entertain the fans.
But here is the thing.
I do not see the killing of Malthael as a proper end of Diablo.
If this is really the end of the franchise, I see another way of closing the story that I think it’s much more powerful: to come back to the beginning of the game, and create a final one using the story of how the Horadrim chased down the three Prime Evils. Imagine it just for one second:
1. Selecting your character from Jered Cain, (Tal Rasha or Zoltun Kulle will not be playable) or any of the other 4 wizards involved. They can create them all just by adding more abilities to the already existing D3 Wizard.
2. Enemy bosses: Baal, Mephisto, and Diablo, the original ones. They also got them.
3. Places: the ones we already know… but anew. Most of the work is done as well.
Once you trapped the 3 in their respective soulstones, once you have lost Tal Rasha to capture Baal, you got to fight Z. Kulle as the epilogue of the story.
If this is not a better end of the franchise than getting your hands on the Angel of Wisdom...