I feel that 4e is missing "soul" that's a very hard thing to describe and quantify, but right now D&D just feels like a hollow shell of what it once was...
The mechanics are good, as it's streamlined and easy to run. But it's things like breadth and depth to characters and the world that I feel is lacking. Perhaps it's that most of the monster manual often seems bland to me. Perhaps it's that I feel that the designers took too much of the safe road in trying to develop things.
Certainly the lack of the 4 other alignments is one aspect of that, and while it's easy to reinstate alignments such as chaotic good, chaotic neutral, lawful neutral and lawful evil with no problem at all, as most of the impact that alignment had hardly affects the game anymore. I think it's the fact that many of the default assumptions feel forced and too restrictive.
Despite their being the ability to mechanically have many things that 3e did not, and that many character classes can do more with their abilities. It just feels that imagination in the game is lacking.
Now I'll say that many of the Dragon and Dungeon articles are starting to fix some of these problems. But it still needs to work things out.
But right now it feels like I have the latest version of Windows that I have to suffer with, where I have to wait until there's a Service Pack that comes along and fixes a lot of problems.