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The dealbreaker for me is something I know isn't even on the table for reconsideration... I want NPCs and PCs to be built using basically the same rules. This thing where level 1 NPC goblins are functionally a completely different creature than any level 1 PC goblin? So much nope.
Yes, I've played games that didn't have that cohesive world rules thing... but then D&D3.0 came out and my group has never looked back. We have a long tradition of characters crossing back and forth between PC and NPC in games, and I'm just not willing to toss that storytelling option into the dustbin for a new edition of anything.
Tied to that is the "the rules work this way for this group of X people and differently for the entire rest of the known universe" stuff that we ran into in this playtest. My group gave up partway through Sombrefell Hall out of sheer frustration so maybe some of that got addressed in later updates, but the different rules for dying/initiative/resonance just grated on everyone. That thing where NPCs/monsters get the same ability as PCs under a different name (trip/knockdown, grapple/grab), but with auto-success instead of needing to roll fooled no-one and annoyed the hell out of everyone.
I personally (not speaking for the group in this paragraph) have some other things that really don't work for me as a player or a GM, but some of those could probably be houseruled into functionality if needed. But the non-cohesive worldbuilding is a hill I'll metaphorically die on.