My take:
1) Get rid of sameness. This is the #1 complaint of my players. Many of them want to jump to Pathfinder and the only reason they are not doing so is because we wanted a campaign to start at level 1 and go to level 30. That and the fact that everyone has spent so much money on 4E books (as DM, I probably spent over $400). A Fighter does indeed feel like other classes due to similarities of powers. Need an area effect, a Fighter can accomplish this. The major #1 offender of this is that nearly all powers are damaging powers. Yawn. My players want many more powers that do not do damage, but affect the environment or conditions of the foes or some such.
2) Bring back durations. X occurs until the start or end of the attacker's or target's round are TERRIBLE game mechanics. X occurs until a save is made is ok, but not all durations should be that limiting either. Allow buff spells that last for various extended periods of time. Allow Wizards to Fly.
3) Go back to few ability classes and many ability classes. In our games, the PCs for players that are not there are played by other players. In 3E, Wizards or other heavy duty spell casters might be harder for someone else to run, but Fighters and Barbarians and Rangers and Paladins and Monks and Rogues and Bards were pretty darn easy for anyone to just pick up. In 4E, there are so many class abilities and feats and powers that every single PC is more difficult to play, especially in combat, unless the player has played that class of PC before.
4) Get rid of dailies.
5) Get rid of milestones.
6) Make Action Points optional.
7) A lot less reliance on magic items.
8) Do not have a 6 delta between one PC and the next on a starting defense and then only raise 2 out of the 3 defenses with level advancement.
9) Better yet, do not have ability scores that rise. This creates problems between haves and have nots as one advances levels. The Wizard still fails his Perception roll at level 30 because the monsters have a better chance to Hide against him than they did at level 1.
10) Git rid of silly healing rules. Healing should not be limited to healing surges cause it does not make sense that pouring a Healing Potion down any creature's throat (PC or NPC) does not heal it. Magic should just plain overrule normal physics.
11) Git rid of silly special PC and monster rules. Monsters have no Healing Surges. Why not? When I have a monster Charm the PC, the PC should be able to heal the monster. The game physics should apply equally the same to PCs and to NPCs. Not just game physics on how fire works, but on how healing and all other game mechanics work.
12) And let a Charm be a Charm. Let a Domination be a Domination. The concept of the PC farting around and not doing everything in his power to assist the NPC is inferior game enjoyment design. Charms should be super serious threats.
13) Bring back real illusions, not game mechanics from other areas pretending to be illusions.
14) Get rid of auto-Identify in the dungeon. The game system is now so magic item dependent that upgrading a character sheet is time consuming plus there are few magic item mysteries anymore.
15) Get rid of temporary hit point class features. A power is one thing. Giving temporary hit points out the ying yang for a class is broken. This basically boils down to avoiding game mechanic class features (i.e. adding a class feature to play with a game mechanic more because the game mechanic exists than because it makes flavor sense for the class). Anytime a class feature is focused on the game mechanics, it's typically a mistake.