I like the idea of support for older settings. Some of those settings have been out of print for such a long time that for a lot of new players they would be something new.
This is why I'd really like to see Mystara make a comeback. It hasn't been supported since near the end of the 2e era, and while I really like those products, the line was cancelled so fast that the Known World never got any major support. Add to that the Savage Coast and Hollow World and you have a unique setting with unique races and monsters.
One could argue that Birthright might be ripe for an update, as well. Yes, they could simply pull the dominion mechanics out of the setting and apply it to the base game, but that wouldn't bring the die hard Birthright fans back into the fold. (I'm not one of them, BTW.) Birthright should not go through another edition without some real
Both Al-Qadim and Kara-Tur are natural expansions to the Realms, which, I feel, is going to be a big deal from the launch of D&D Next onward. I don't think the Realms will be only getting three books this time around. Maztica would be in this category as well, but if WotC keeps the current timeline then Maztica fades into oblivion.
If WotC created a new setting that combined the best parts of Planescape and Spelljammer, I wouldn't complain. Purists might want the original settings, but I don't think that's going to happen. (I'd buy them.)
I think the best setting for WotC to get behind, besides the big three*, is Ravenloft. The mainstream market is vampire and werewolf crazy right now. And as long as the designers stay true
to the origins of the setting, it could become as popular as the Forgotten Realms (including board games, novels, and CRPGs).
Imagine a Ravenloft MMO. A grim horror game with the classic concepts of golems, vampires, werewolves, etc. A video game that is more about fear than power-gaming.
*Forgotten Realms, Dragonlance, and Greyhawk. (Personally, I also put Dark Sun into this category.)