My comments, with no particular order or organization:
The item tables are horribly inconsistant with the notion that magic items should be rare and not something easily bought or sold.
The tables with origins and quirks and properties are great.
The new magic items seem kind of boring to me. Maybe it's just presentation, but nothing listed there seems like something I really want my character to have.
I don't like that wands and staffs are back to "hurr free spells!" rather than being used to channel the caster's power as they were in 4e.
At Will spells shouldn't require and use the spells per day system, that's silly and inelegant.
Casters are too versatile. Being able to have so many spells known (indefinite but high number for wizards, all for clerics) makes casters capable of defeating just about anything the DM throws at them with just a good night's sleep. Especially at high level. It's also a big part of what relegated other classes to support roles or irrelevance in 3.x. And it reduces caster customization, since why would you choose to have one thing or another when you could just have everything?
Use of expertise dice is excellent (in particular Sneak Attack integration), but some maneuvers still need polish. Skill check additions are good - especially Mighty Exertion, which addresses the "Hercules could split a mountain!" argument for fighter power nicely. Or it would, if you got rid of the "highest die only" limitation, which needlessly gimps martial characters and shouldn't be in any of these maneuvers.
Whirlwind Attack is outright better than Cleave, which is bad. Glancing Blow is ridiculously bad - you will hardly ever miss with a roll of 10+. Also, only using the highest die result is a pointless gimping of an ability that wouldn't be that impressive even if it was available on every miss. Vault would make more sense if it added feet to a high jump too.
It's redundant and silly for each specialty to end in the word "specialist".
What's now "Arcane Magic Specialist" was better when it could also be applied to non-caster characters to give them a touch of the arcane. The metamagic ruins that. Divine Magic is better off, but the healing feats aren't conceptually versatile and are a bit redundant conceptually with the Healing Specialist.
Both ____ Initiate feats were far better in previous versions.
Feat effects shouldn't have "if you rolled X or lower, treat the die result as if it was at least Y" effects. They're too much hassle to remember. Stealthy Escape's "disadvantage that can't be canceled by advantage" also sets a bad precedent for non-advantageous complexity.
Some skills seem needless. Use Rope? Really? That was never a good idea. And splitting spot/search/listen just needlessly complicates things. Although honestly, that stuff might be better divorced from the skill system entirely.
A lot of equipment numbers are still needlessly unrealistic. A ten pound greatsword? This was acceptable for TSR when they were a tiny company with no budget, but Wizards could pay people to look this up even if looking it up took more than just typing the weapon name into wikipedia, which it doesn't.