Taking Zak Smith's lead, here are a few pitches for how WotC can approach old D&D settings for 5e.
Rather than being a painfully generic fantasy setting, have the Nentir Vale books be a series of toolkits for creating a custom sandbox campaign, such as cities, forests, underdarks, etc. No two Nentir Vales are the same.
Another extremely generic fantasy setting that could be greatly improved by turning the crazy fantasy tropes up to eleven. This would be the setting that appeals to Dungeon Crawl Classics players and Adventure Time fans.
More sci-fi than fantasy with Moebius and cosmic superhero comics being a main source of inspiration. This is the best opportunity to show that the 5e ruleset can be used for genres other than medieval fantasy and should lead to other settings in unusual genres.
The multiverse is a mess of portals, time tunnels and tears from magic spells; jumping from plane to plane requires more luck than intention. Adventures in this setting should feel like a season of Doctor Who with the TARDIS having a completely fucked-up navigation system.
You can play the setting game by following these rules:
Tell WOTC how to renew their settings for 5th Edition in two sentences or less. You have to do at least three settings. Extra points if it seems like something they might actually do.