Well, I can't really see too much of a departure from the current rules set: 4E may very well be a dusting off & polish of the current 3.5 set, including new rulings (such as with polymorph), & perhaps the inclusion of a few new elements like Action Points, reserve feats (ala Complete Mage), & the like.
I'd really like it if 4E went the way of the generic classes from Unearthed Arcana (to allow for rather easy customization), going with a Talent tree system like d20 Modern (with many, many prestige classes covering a lot of old PrCs & base classes) that encourages multiclassing. Perhaps something along these lines:
- Warrior: Best BAB, Good Fort save, d10 HD, bonus feats; talent trees focused on fighting styles/combatant concepts (knight, swashbuckler, samurai, archer, berserker, etc.)
- Expert: Average BAB, Good Ref save, d8 HD, bonus skills/skill points; talent trees focused on special skills/abilities (thief, bard, ninja, scout, assassin, ranger, etc.)
- Adept: Poor BAB, Good Will save, d6 HD, spellcasting/power use; talent trees focused on various types of magic/power use (arcane, divine, psionic, invocations, prepped magic, spontaneous magic, etc.)
Also, maybe shifting Alignment to a more Alliegiance-like system (also from d20 Modern), in a manner to potentially help deal with some issues/arguments regarding Alignment for some players.
I still see Greyhawk, or some other genericized background setting, as the defualt setting for D&D, esp. with the named spells & all that. Worlds like FR and Eberron add a lot of unique elements to D&D in their own right: it'd be easier to add elements to a game than subtract them for beginners. However, I could feasibly see races like changelings and shifters maybe working their way into the core game, since the concepts are rather basic enough to include for any world (in an aasimar/tiefling/feytouched/genasi type of heritage sort of way). Perhaps kobolds becoming a core PHB race as well (thanks to the whole dragonish heritage thing).
But, other than that, I honestly can't say what the future of D&D may look like. May be very similar, or may be quite different. Don't know.