Now. How does one up the ante in the Diablo universe at this point? We've defeated the Lords of Hell, leaving Hell powerless. We've saved Heaven. We've saved an invasion of the planet from Malthael. Really, what else IS there? Well, saving the universe, of course! Inarius is going to be hating everyone and everything at this point. But how will he threaten reality without the Worldstone? Is there something else he can use?
They've set it up so that the next antagonist is probably going to be a Nephalem (or a group of Nephalem). The Nephelem used to have god-like power and that power has started returning with the destruction of the Worldstone.
That said, the Prime Evil Diablo has been released as of the end of RoS, so there's also that.