I'm saying it up front - this is an unfair review (and when I'm willing to admit it, you know to break out some extra grains of salt). I've only read the Player Handbook and made one character for Dave's soon-to-begin online campaign. I do not yet have any actual play experience. I intend to make another posting after the online campaign has gone on for a while and re-review the game.
That said, I don't like what I've seen.
To me, the biggest issue for tabletop gaming is: in what way are you better than your major competitor, a video game? Frankly, if I want to team up with four other people and kill a dragon, I can do it with a lot more visceral excitement in Baldur's Gate II or World of Warcraft; I won't have to do a lot of fiddly arithmetic, there's almost no down time (compared to tabletop games, which have sometimes been called "ten minutes of fun packed into two hours"), and there are even visuals.
So if those are the relative strengths of video games, what do tabletop role-playing games offer? First and foremost, infinite options. You can go "off the beaten path" in a conventional RPG with a GM in a way that's, so far, totally impossible in a computer game. Second, meaningful and real story-telling. You can get this in some CRPGs, but it's never "your" story - you don't get to be a writer or even a co-writer. Third, a focus on the inside of your character's head, instead of on repeated physical conflicts: the "easiest" form of conflict, and therefore one used almost exclusively in CRPGs.
So, to me, D&D 4th heads strongly in every direction in which CRPGs have their relative strengths, and away from every direction in which tabletop RPGs have their relative strengths.
There's little to support a meaningful, believable, or engrossing world, certainly compared to other tabletop games like Reign or Exalted. A huge proportion of the book is taken up by long lists of character powers, which is about as inspiring as doing a database search for mage spells on wowhead.com.
The game mechanics have almost nothing to do with who your character really is. If you look at, say, a GURPS character sheet, the combination of the advantages, disadvantages, skills and quirks will paint a picture to the reader of who that character is and how they would act. Likewise, Spirit of the Century's Aspects, Reign's passions, and even Exalted's Intimacies, Motivation and Virtues. D&D 4 has next to nothing; the only one I can think of is Alignment, and even those have been pared down from the classic 3x3 matrix!
In addition, the mechanics that do exist are focused almost exclusively on combat. It is, essentially, impossible to create a character for whom the majority of their abilities are not centered around killing other people, and almost all of the rules revolve around fighting.
To me, despite the obviously high level of polish and implementation skill, which I would be remiss to not point out, the very design intent of the game was a serious mistake. I already own Descent: Journeys in the Dark (to say nothing of World of Warcraft); it's a better game when I want to sit down and slug it out in a dungeon. I already own GURPS, Reign, Exalted, Spirit of the Century, etc: they're all better games when I want to actually role-play.
Where then does that leave D&D 4?