Having the different classes interact with members of long-running factions like the Priests of Rathma or the Crusaders could be a good way to both move the narrative forward while also referencing game's past D2R ladder items. Especially with Deckard Cain dead, players will need new places to learn more about Sanctuary's deep history.
A large chunk of the expanded media focuses around the Eternal Conflict and the Sin War. The former is more well known to casual fans, and the battle between Heaven and Hell has long influenced the overall story of the Diablo games. The Sin War is really only dealt with in the books and comics, but is equally important. Lilith and the angel Inarius had children together: the Nephalem. Nephalem soon grew to become more powerful than the angels and demons that created them, and that led to a war between factions that saw them as threats to Sanctuary. That conflict spread and could have big implications in Diablo 4.
It's possible that long-running tensions that have been explored throughout the various expanded media could come to a boiling point in Diablo 4. Angels are powerful forces for good, but often only their own version of what good means. Many of the angels believed the Nephalem should have been destroyed during the Sin War, and their return to prevalence in Diablo 3 could lead to a conflict with Heaven itself.
That might seem far-fetched, and it's just one of the many possibilities for Diablo 4. There are so many threads left to pull, even after most of the Evils have been defeated. Hopefully, fans will get a more comprehensive look at Diablo 4's story soon buy d2r items, as it definitely has a deep well to draw from.
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