I feel like D4 will be an entity that will not target veterans of the series like me who want it back to its grimdark roots focused on a tale of a small band of adventurers. D4 has to top everything that its predecessors did, and do so for a wide audience. It's going to be an epic-scale story between the forces of good and evil. The world would be explored even further, and we take the fight into new levels of heaven and hell like we've never seen before, maybe even to the cosmic level of fighting gods or something. I just don't think it can turn back to anything simpler now that we've done things like kill angels and we've been able to kill all the prime evils as the exist here.
What I'd actually want to see is a sidestory taking place in the Diablo universe. Something like a Dark Souls style game, maybe a prequel playing as the Horadrim and using archaic forms of weaponry and magic that aren't culturally specific. I think there's a bittersweet charm to the idea that you would be playing a character that fights a secret war against the demons, and is completely unknown to the world. Introduce an underground network across the world where the Angels appear in secret, operating different anti-demon organizations that would either join up and form the official horadrim, or be consumed in the process.