Just have a game clock where each sidequest costs a certain amount of time units to complete, and then plot things happen when the clock hits the next threshold. Players would then have to figure out which quests they actually want to work on in the time they have. It’d keep the story moving and add replay value (by forcing shorter completion times, but you can’t do everything in one pass).

It could even be as basic as completing a quest moves you to the next day, and some of the quest markers and npcs have simply gone.