Haven't seen this one yet:
Skill Challenges are not conducive to roleplaying (I'm talking about the social aspect of the adventure, not when the skill challenge is merely physical). Yes, there is a big example in the DMG on how the players try to influence a ruler. But why do you need (for example) 6 successes out of ten rolls to achieve that? Why doesn't the DM simply decide beforehand which arguments will have merit, which will be counterproductive (talking in a very general sense, obviously, the inventiveness or craziness of the players cannot be factored in completely), have the characters roleplay the conversation and if necessary use one roll with modifiers to see whether they achieve their task? Skill challenges as they are conceived of now are just disguised dice rolling fests.
Upping starting level hitpoints is a good idea - no one new to roleplaying relishes the idea of playing a weakling who cannot survive one encounter. But upping eveyone's hit points while reducing damage output is the very opposite of fun, and fairly guarantees combat lasting as long as it did before (or even longer). Which defeats the whole 'more fun, less chores' approach which apparently guided the design team.
Speaking of which: marking? Who demanded this to be in the rules? The designers or the playtesters? To me, this is a wholly unnecessary new level of complication. Just like tokens were a new, overcomplicated mechanic in Iron Heroes.
Some of the powers are stupid and have bad names ( the pit fiend's Irresistible command, for example). Others are cool, still others are meh.
Narrowly defined party roles are dull, limiting and pointless.
D&D no longer resembles fantasy fiction in any way or form save for basic subject matter. It's become its own thing completely. Which means that it's harder than ever to try and approximate the fantasy fiction experience with it.
The monster selection in the MM is bizarre. I don't miss the descriptive text - it was always hideously badly written and a waste of space. Especially since every creature is illustrated clearly (and a picture says a thousand words

). However, the absolute lack of story hooks and ecology make it a dull book (unlike the Iron Kingdom Monsternomicons, for example, which simply scream 'use me'!).
Too many changes were either ill-conceived or change for change's sake. Not necessarily with regards to 3e but with regards to D&D itself. Not that some changes weren't necessary or desirable (and some of the changes implemented are good ideas). But they went overboard and I am sure that in the months to come many quirks and problems will be discovered which were unforeseen.