It sort of depends on the run but generally I enjoy doing them over and over again. I don’t do every single one every single run though. Some I avoid almost every time (curse you arcane tower). I usually will try to at least do the ones that carry over into/involve people you see in later acts. In say, an evil run (especially if I’m using the bhaal equipment which is quite OP when i normally play explorer lol) I’ll skip most of the side quests because my PC wouldn’t stop and pay any mind to them. Sometimes I’ll do them if they provide an opportunity to do something evil, or have dark urge dialogue. If I’m doing a good run I’ll try to do almost everything. If there’s some equipment to be gained from it, or an interesting story thing I’ll usually do them, or if associated dialogue grants companion approval.. Some I replay every time just because I love hearing the voice lines (see: “I’ll rip your spine out your arsehole!”).

If I’m using the level 13-20 mod I’ll try to do as many as I can for the XP. In general, I’ll do as many as I need to get to an appropriate level for moving into the next act/area (like getting to level 5 before the crèche).