Note: this is not based on actual play time yet, just on reading over the rules.
I suspect that 4E is going to get a lot of grief. It's got a hell of an act to follow in 3E. To some extent, I think that the success and overall excellence of 3E are the biggest problems that 4E has, because where it fixes a lot of the problems in AD&D, it does so by skipping over 3E's solutions and finding its own. As an example: 3E had an elegant solution to fixing the multiclass imbalance: every character can level in every class if they want. Want a level of cleric? No problem! 4E solves it in a completely different way; every character has exactly one class, but you can take a special feat to gain some abilities of another class.
To be honest, I think that 4E would have gotten a better reception if it had followed AD&D2 directly. It has, in some intangible way, more of an original D&D feel than AD&D did, but in a streamlined way.
Okay, enough 2E/3E comparisons. How is 4E on its own? Personally, it looks pretty good. The system fixes several of the major problems with every edition of D&D printed, such as the uselessness of first-level characters and the cleric being nothing more than a walking first aid kit with a 'turn undead' ability. Above all, it looks fun. They've clearly tried to give all the classes interesting options at every level, and to make it so a poor decision early on doesn't cripple the character permanently. I'm not sure I care for the Heroic-Paragon-Epic path design, but I'd need to see how they play to really make a judgement.
I'm not 100% sure I like their initial class choices - Cleric/Fighter/Rogue/Wizard are obviously all required, and Paladin/Ranger seem reasonable. Warlord is an interesting choice - a battle leader who helps those fighting with him. I don't think I've really seen anything quite like that since Military Scientist back in Dragonquest. Warlock...I'm surprised they printed. Clearly things have changed from the 2E days if they're willing to print a class that explicitly makes pacts with extraplanar entities for its powers. I'm surprised at the lack of the Bard and Druid classes, especially the Druid. (I'm sure we'll see them again in supplements soon enough.)
The racial choices, though, I can support. Gnome and half-orc are gone, and I (personally) won't particularly miss either. Gnomes seemed lost without a dedicated illusionist class (gone since 2E) - without that, they're just variant dwarves - and half-orcs always felt like they were meant as an NPC race. Instead, we get three 'new' races, the dragonborn, eladrin, and tiefling. Tieflings we've seen before - planetouched humanoids from the lower planes. Having them as a core race is (again) an interesting choice - I'd have expected aasimar (their upper-plane counterparts) as well, but they aren't even in the Monster Manual. Again, we can clearly see that the 2E self-censorship has gone by the wayside. Eladrin aren't quite what they used to be (the core chaotic good planar beings); now they feel like a more magical variant of elf, where the main elf race has become more sylvan warrior-oriented. And dragonborn tie the players into the dragons of the title more closely than ever before in a core race. The Monster Manual has the basic info you'd need to re-add Gnomes, plus Drow, Orcs, Warforged, and more.
Mention of the Eladrin brings up another change, one that I'm unsure if it's a good thing but it's certainly interesting to see what they did. Alignment has been simplified and streamlined down to five choices: Unaligned, Good, and Lawful Good (as player choices), plus Evil and Chaotic Evil for the villains. Lawful Good and Chaotic Evil mostly fill in the slots they covered in the original 3x3 grid; Good covers both Neutral Good and Chaotic Good, while Evil covers both Neutral Evil and Lawful Evil. Unaligned is the most interesting one, covering both variants of Neutral ('working for balance' and 'don't care') plus Lawful Neutral and Chaotic Neutral. Unaligned isn't really Neutral, though, because it's more 'good vs. evil is nice, but I've got a job to do'. The bit I find most interesting is that Unaligned acts as a wildcard in matching deity and worshiper alignment - an unaligned worshiper can worship any god, and any alignment can worship an unaligned god. This works well for (as an example) a God of Magic, who may get worship from wizards of all alignments. On the other hand, it seems odd that a Lawful Good deity (Bahamut, the honorable paladin god) would accept an Unaligned worshiper but not a Good one. This may be something to tweak as a house rule.
Other things: I like healing surges. They're perhaps a bit on the generous side (1/4 of your HP, 5-10 times a day?) but they (along with the higher starting HP) make it possible for low-level characters to be a bit more daring without worrying about instant death from one lucky sword swing. I like encounter-frequency powers, and at-will Magic Missile that needs a to-hit roll. (Hey, wizards aren't useless after they cast their one daily spell! What a concept!) For that matter, I like at-will cantrips and other low-level magical abilities in general. I like ritual spells - a way to handle those utility abilities that don't involve burning spell slots. I like that almost no classes start with proficiency in plate armor. I like the idea of holy symbols, rods, and staffs as class implements, where an enchanted one can improve your ability to use your class abilities just as an enchanted weapon.
Overall, I'm pleased with the design. I suspect that it may have been (oddly enough) an even better game if they hadn't had the D&D baggage that they needed to use, but if it had been just another RPG system, nobody would pay any attention to it. For good or ill, D&D is still the 800-pound gorilla of the RPG world, and this appears to be a good version of it to go forward and bring in new players.