For certain quests you need to talk to certain people, but those people are gone (marked in the bottom right corner of the map) because of the main quest.
The quests for which I’ve noticed this are Restless Spirits (the quarrymen, though this can be bypassed) and the Cuman roadside bandit quest with Matthew and Fritz (for which some old woman is gone).
Additionally the “devils” that attack the witches during their Sabbath (in a quest from the Uzhitz priest), if you don’t kill them can be found just outside the map on the road to the north of Skalitz, they’re just standing there. If you shoot an arrow close to them they’ll come running up to you and the weird part is that you can’t loot them.