I think the boss of the next D3 expansion will be Diablo. When you fight Adria, she tells you that she has set things in motion to make sure that Diablo is reborn again. Now the thing is, clearly the nephalem are more powerful than either Demons or Angels, we've proven that. So how can Diablo compete?
Well, nephalem are so powerful because they are a mix of angel and demon. At the end of the fight with Malthiel he absorbs the black soulstone, basically taking in Diablo's prime evil self. Then we defeat Malthiel and Diablo's soul is free...but we know he absorbed the other prime evils, why not absorb some of Malthiel as well? Making Diablo into a Nephalem.
Now he can compete with the hero on equal footing. Diablo can now recruit other humans, awakening their nephalem abilities somehow, and try to take over. Or maybe he just starts slaughtering whats left of the demons and angels, somehow taking their souls and mixing them to make a nephalem army.
And in the end, we'll only defeat him thanks to those meddling kids...err, I mean, Leah's soul, which is either freed and she helps us by giving us information on Diablo's new form, or her soul is still trapped within Diablo (maybe he takes on her form when he manifests as a nephalim? At least initially, before becoming some big bad boss for us to fight), and from within Diablo she helps us to stop him.