I like almost everything WotC is doing with 4E, and would likely do it similarly, with two (unfortunately major) exceptions:
(1) The major changes they're making to "D&D brand fantasy." Tieflings and dragonborn as core races is almost certainly losing them customers. (Is warforged core? If so, that's another one.) These things, especially as conceived and shown in the art we've seen so far, are just too far from traditional D&D. Effectively, if people want to use all of the core rules, they're forced to begin entirely new campaigns. It's probably a good idea to begin a new campaign with a new edition, but forcing it is inviting players not to buy into 4E.
If it were me, I'd have stuck with the races of 3.5, with the possible exceptions of gnomes. (I'm not a gnome hater, but honestly the only gnome characters I've seen in the last four years of 3.5 have been the ridiculously over-powered whisper gnomes.) I do like the split of elves and eladrin, however; most campaigns I've played in already have a division between "magical elves" and "hippie elves." I also think you could add shifters and changelings pretty easily, as long as suggestions were made for introducing them to existing campaigns in a subtle way, and that's not really hard to do for those races.
You could also argue that the cosmology changes are too much, too fast, but I've rarely played in a game where it mattered whether the planes existed in Great Wheel form or not, so I don't think that's a major stumble.
(2) The 1-1-1-1 rule. This single rule -- and the change in mindset that its existence indicates -- is what will keep me from ever playing 4E. I'm an abstract thinker, but this rule's just more than I can look past, even with a lot of effort. I think this rule demonstrates a lack of respect for the intellect of gamers, and a fundamental misread of what people actually want.
(The poll here on EN World showed twice as many people would rather keep the 1-2-1-2 rule for movement, and hexes actually got more positive response than 1-1-1-1. Even if you discount those numbers some because the poll is self-selected, and even if you (almost certainly rightly) assume that it's less of an issue for most objectors than it is for me, it remains a tremendous bungle. In an edition that it stressing mobility and fluidity in combat more than ever, it is remarkable that WotC would deliberately introduce such huge inaccuracy in movement distances and tactical map layout.)
There is a third issue, but it's one that I only raise as a player-designer. If I were designing for WotC, I think they're doing it exactly right. Namely, the creation of "powers" for all character classes. WotC's best-selling books in 3.5 have been "modular crunch": feats, spells, tricks, martial maneuvers, vestiges, mysteries, prestige classes. Now they've created powers, an entirely new -- and undoubtedly huge -- new class of modular crunch with which to sell books. Every single class will have lists of new powers, to go along with the rest of the stuff I listed, in new books.
It's very savvy business. I don't much like it as a player, but the truth is, I bought every bit of it as a 3.5 gamer, and if I were going to 4E, I'd buy every bit of it there, too. And that makes it brilliant design, from a corporate perspective.
If I were designing as a player, I'd make things more constructed ... this "power component" moves an enemy, this power component imposes a condition, this power component helps a teammate in some way, and you build your powers yourself from those lists. But, again, the problem with that approach, from a corporate perspective, is that once the players have the power components they aren't going to buy lists of powers. Sure, you might be able to squeeze out a book of power components, but that's pretty much it ... no milking it, as 4E splatbooks will do.