I really don't understand this sort of concern. As a BSEM-1st ed-2nd ed-3rd ed gamer with a fondness for all things Greyhawk, I don't expect to have any trouble at all running 4E games in the Flanaess, or anywhere else. I have homebrewed multiple campaign settings, none of which are going to give me trouble converting to 4E. Most of the campaign settings I've written or read change the default assumptions from the PHB. This includes Forgotten Realms, Planescape, Pathfinder, Dragonlance, Ravenloft, and many others. These games fail to collapse under the weight of their idiosyncrasy. People can and do play games that barely use the PHB's implied setting, races, classes, and the like. They are easy to remove and easy to replace.
Considering that they're supposedly planning to release a campaign setting each year for at least the next few years, I expect that they've designed the core game to be friendly to the sort of demands that settings make on the core rules. Eberron, for example, is still going to be Eberron, without even a timeline shift to alter continuity. I survived the changes from AD&D 1st edition to 2nd, and then 2nd to 3rd. I have no reason to believe I will somehow be drowned by the coming tide of 4th edition.