Here's a few examples that I can currently dig up (picking many off ENWorld's news site at http://www.enworld.org/index.php?page=4e ):
- Standard Races & Classes in the PHB are being totally altered. Apparently out are gnomes, half-orcs, barbarians, druids, bards, monks, etc. In come tieflings, eladrin, warlords, and warlocks. (As I may point out several times, compare the continuity of 1E->3E to this lineup in 4E.) Paladins can be any alignment, etc.
- Wizards don't memorize daily spells anymore (also called the "Vancian" magic system). Instead, they have fixed, "siloed" powers -- some usable every round, some every few minutes, some once a day. They have some kind of "weaponized" accoutrement whereby they have to arm themselves with an orb, scepter, staff, or book to cast spells. There's a designer quote that "Wizards will be able to cast 25th-level spells." And I guess Fighters have similar Powers themselves that work kind of like magic (as seen in some late 3.5 supplements).
- Classes aren't categorized by the classic four primary classes anymore -- you've got these 4 "Roles" which categorize classes by Leader, Defender, Striker, or Controller (for some reason).
- 1st-level characters are designed to be inherently "head and shoulders" above normal people in the world. (Presumably like Star Wars Saga starting 1st-level PCs off with 3 Hit Dice). Levels are said to come faster but make less of a difference from step-to-step. PHB goes from levels 1-30, which a lot of people are saying cover the same "sweet spot" as classic levels 4-14 or so.
- Saving Throws no longer exist. Instead, you've now got fixed defense scores (like magic Armor Classes) that magical enemies roll their attacks against.
- There's some kind of "condition track" whereby lost hit points degrade your abilities (creating, I suppose, a kind of "death spiral"). Spells are being totally revised; fireball doesn't do d6/level damage anymore, for example. Save-or-die spells are gone, being turned into hit point damage that triggers the condition track (it appears).
- The D&D cosmology of the "Great Wheel" is wiped out and replaced with totally different, new stuff. There's a new division between devils & demons -- demons are actually some sort of corrupted Elementals, now, I guess.
- Magic Items don't have prices or rules for PC construction, apparently (a great tool in 3E).
- Challenge Ratings are gone (another great tool in 3E).
- Alignment is heavily revised, apparently.
Anyway, I could go on and on and on. Suffice to say that lots of the shared experiences from OD&D up through 3E are being wiped out and replaced with completely different mechanics. (Which is even more disturbing when you compare 30 years of development and fine-tuning to the very rushed time constraints that the 4E writers seem to be under in late 2007.) Let me pick out one illuminating quote from the designers:
You can't really just convert a character directly from 3e to 4e. We pretended you could do that from 2e to 3e, but that conversion book was pretty well bogus. The fact is, as I explained it a lot at GenCon, that your character isn't what's on your character sheet: your character is the guy in your head. The character sheet is how the guy in your head interacts with the rules of the game. The rules of the game are different, so you'll be creating a new implementation of that character, but the character needn't change much.
(That's James Wyatt writing in his blog here: http://forums.gleemax.com/showthread.php?t=906388 ). Got that? It's actually impossible to convert a character from 3E to 4E. While there was a widely-used conversion book published for the 2E->3E switch, the designers are saying that no such conversion system is possible from 3E->4E. The best you can do is to take the general "feel" of your character (or monster or adventure setting) and reconstruct it from scratch in 4E. That's definitely a first, as it wasn't the case in any previous switchover points between versions of D&D -- that's just how different 4E is from anything that came before it.
There are stories from playtests where monsters have thousands and thousands of hit points, clerical healing fires off automatically at the same time as they attack, and the players feel like they're playing a completely brand new game and have absolutely no idea how something as simple as a goblin or a zombie is going to function against them. And the designers are trumpeting all of this as specifically a good thing. Me, I think it's a bad thing that you can't use all your preceding understanding and materials for D&D at all anymore.
One thing I'll say is that this "accelerate the changes" mode of designing is very much consistent with the movement I saw in the 3.5 Revised rules (which I also skipped). At that time, I identified the rather encyclopedic changes to the spell lists as radically more different than all the changes from 1E->3E combined (see my report here: http://www.superdan.net/down3-5.html ). In my opinion, it seems like 3E made some noticable changes to the game; 3.5 was a test to see how widespread changes could be and still have acceptable sales (with ever-accelerating changes through later supplements); and 4E is finally embracing an entirely different kind of game.