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Default/Hard to Excise Grid Requirement.  Let me make one thing clear: I like using the battle grid.  Sometimes.  But I also like the ability to play a pick-up game with character sheets, a dice bag, and some sort of box lid to roll on, and have had some pretty amazing sessions that only worked because I was able to run TotM combats.
Threat: Negligable.  Devs seem focused on supporting TotM

Default/Hard to Excise Encounter Paragdim.  I like the freedom to be fluid with encounters, something that I didn't feel 4e did a good job of delivering.  The push to distinct, bite-sized encounters with the ability to rest between each one a standard expectation put a crimp in the style of active dungeons.
Threat: Low.  "Short Rests" are in but right now only for HD-based healing.  Devs seem to be focusing on adventure-as-unit

"Dude, Where's my GDSM and Amulet of Reflection?" ~or~ Magic Items as part of Character Build.  The game should be playable without magic items.  Characters should not plan ahead for *specific* magic items even in campaigns where magic loot of some description can be safely anticipated.  If Magic Items are part of Character Build and I somehow run the system anyway, I will have Santa Claus show up to deliver the Player Progression Loot like a scene out of Narnia (but played for spiteful humor)
Threat: Low.  There's been a lot of talk about flat math and magic items being magical, not math fixes.  However, I think that's kind of been a "love it or hate it" proposition, with some demanding exactly what I don't want to see.  Time will tell if the devs change their tune.

Critical Mass of Stuff That Makes My Brain Hurt.  Proning oozes.  Bleeding Skeletons.  Burning Fire Elementals to death.  The sort of things that shouldn't even work with magic involved (I'm not going to dip so much as a toe into the martial versus magic logic argument here).  A little of this isn't a dealbreaker; It's practically inevitable as the rules make a lot of round holes and specific situations throw out a lot of square pegs.  A lot of it is.
Threat: Moderate.  Current design talks the talk ("For conditions, we want to think first about what's going on in-universe") but doesn't quite Walk the Walk (Ray of Frost versus Flyers, for instance).

Everybody Resource Manages the Same.  A more accurate way of stating the complaint that "All classes are the same" under early-4th ADEU.  Different classes, or at least different castes of classes (Power Sources, if you will) should have different mechanical skeletons on which they're built.  Especially with Themes and Backgrounds providing a lot of your surface differences, the classes need to be unique to their cores.
Threat: Moderate.  Right now we have Vancian (Wizard), Weirdo psudeo-Vancian (Divine), and ??? (Martial), but I'm prety sure there's a ton of support to sliding towards ADEU, and I'd really like to see Arcane and Divine drift farther apart...