I always thought the signature setting for AD&D was Dragonlance. I didn't much care for it, prefering my own home-brewed world, but they sold a lot of dead trees in both game supplements and novels.
Mm... more novels than supplements, I think. Dragonlance started out as a series of D&D adventures, but the novels soon came to dominate the line. I never had the impression that the setting was a big draw as far as gaming went, although it had its adherents and still does.
If one measures strictly on popularity, of course, Forgotten Realms walks away with it. I'm fairly sure neither Greyhawk nor Dragonlance ever held a candle to FR in terms of sheer player mass. But Greyhawk was the "core" setting, the one whose influence pervaded the rest of the game. Look at all the PHB spells named after Greyhawk mages, for example. What were (still are) the most well-known artifacts in the game? Vecna's Eye and Hand. Little bits of Greyhawk flavor were everywhere.
I think the problem with yet another setting is dilution. Just in terms of 4e alone, we have: Dark Sun, Eberron, Nentir Vale, and Forgotten Realms (plus Neverwinter), not to mention some less-defined settings such as the city of Sigil, the shadowfell, and very likely Ravenloft in the near future. The possibilities available with those settings alone are pretty huge.
I see your point, but at the same time, I think 4E is really in need of an infusion of new creative energy on the "fluff" side, and I would like to see a setting not shackled to the ghost of TSR (or for that matter Keith Baker). You suggest, for instance, a pirate-themed sub-setting of Eberron for the "island world" concept; but I at least would never buy that, because I don't have any interest in Eberron.
And even if I did, Eberron's been done already. The thing I think WotC has forgotten about D&D is that firing the imagination of players and DMs is crucial to the long-term success of the brand. And that demands new material from time to time, not just old stuff warmed over. Dark Sun was my all-time favorite setting back in the 2E days, I was very happy when they released it for 4E, but y'know what? It doesn't inspire me now the way it did back then. I've been there and done that.
It's also worth keeping in mind that part of what sank TSR was the insistence on
supporting a bajillion settings, with lines of adventures and supplemental material for each one. WotC has largely avoided that, so I think they have room to branch out a bit. I might never run a campaign in the "island world" setting (I'm too wedded to homebrewing), and I'd be highly unlikely to buy a lot of sourcebooks for it... but I'd buy the boxed set just to read through it and see what it had going on.