How did things work out for Roche? How did Nilfgaard’s conquest of the North unfold? Did the Lodge of Sorceresses manage co claw its way back to power? And whatever happened to Iorveth and Saskia?
The Witcher 3 left quite a few story lines open-ended. Whether that was done with the specific aim at a new instalment in the series or not, The Witcher 4 won’t be lacking in threads to pick up.
Continuity is key here. Many of the storylines seem to be invalidated by player choice in the previous games, but they don’t really have to be. Taking Iorveth and Saskia as an example, helping him break the spell on the rampaging dragon is as viable a quest as putting said dragon down in an epic battle.
One possible avenue to explore, apart from the ones already listed above, is the fate of the witcher schools. Building them back up Jedi Academy style could make for an interesting part of the story, and carving out a place for witcher in a changing world could be a dramatic experience.