Oddly, despite agreeing with many of the criticisms here, I think my biggest three problems are something no one else has complained about:
Quest XP rushes the PCs through a level. What I mean by this is that, fairly often (especially in pregen adventures), the major quests involved are all going to be completed at the end (or near the end) of the adventure. This means that for an adventure that runs, say, from 11-14, the PCs spend a good bit of time at 11, a good bit of time at 12, and hit 13 and 14 fairly closely together. I really, really like the Quest XP mechanic (and it helps to keep my group focused on their story goals from week to week), but significant quests seem to produce this "Bam! You level up!" effect.
I think someone mentioned this one, but: The solid, well-structured mechanics of the rules (despite complaints, they are fairly robust compared to many systems, that may not even consider any attempt at balance), often mean that my players ONLY choose to use their powers. They have cool powers. They have cool cards for them. Thus, that is all they do. The accessibility of the rules, and the ease with which people can grasp the tactical implications of their powers and feats, has led them to ignore the "reality" underlying those rules. When the troglodyte casually kicked the sunrod into the underground river, throwing the whole party into darkness, my group just about freaked. It was like he suddenly manifested this ability to create a Zone of Darkness! They seldom bother with all of the tactical options given to them by terrain, environment, and objects in the game. Instead, it's all positioning and powers.
Too many Feats. Characters have a limited number of feat slots, and the existence of so many feats puts pressure on them to just select the 'most powerful' ones which will be available most of the time. In addition, the constant addition of more feats means that a player will often feel that a new feat does a better job of representing his character than an old one. Also, the complex interaction between multiple feats again forces a lot of hard choices and regrets. I think that feats should have been 'reigned in', and kept as consistenly minor bonuses, deliberately designed not to interact and trigger off each other so much, and not been such an essential part of many builds. The 'math fix' feats make this really bad, as they are putting even more pressure on limited feat slots, but they are also really bad feat design. +1 to three defenses? That's a feat? I thought that the feats were designed to be minorly useful especially when static. I would like to have seen feats been kept more minor in scale, and perhaps given out each level. That way, there would have been fewer "must have" feats, and more opportunities for feats to customize characters without penalizing or rewarding certain choices with awesome combat prowess or minor situational benefits.