Region quests are typically part of storyline and combine multiple sub-quests towards a certain task(usually killing the region boss or unlocking something). They're often mandatory and can't be declined.
Some ideas:
1.Reduce back-and-forth movement for sub-quests. Fetch quests don't sound impressive for region-level quest.
2.Key quest content should be instanced. Quests of any importance should be fully-instanced, open-world interaction is detrimental to immersion(quests are single-player adventures).
3.Quest must be difficult enough but provide progress for each completed part.
4.No failure condition. Region quest is usually mandatory to move the storyline forward, but can be disconnected from other regions quest(equally important regions model vs linear storyline)
5.No optional side-quests inside, all sub-quests are integrated as part of region quest.Don't waste players time.