Hussar
Legend
In addition to FR and Greyhawk (and Dragonlance) not being that distinct from each other to the average person, I don't think that Mystara was that distinct either. Between FR, Greyhawk and Mystara, they were the general settings of certain editions or variants of the game system, whatever general elements were introduced to the game they were just dumped into those settings. Kara Tur was originally intended to be in Oerth and the Greyhawk setting, until it was actually placed inside of Forgotten Realms.
I also don't think we can use UA to go by what they might release, since after all they did have that UA on Modern Magic a while back ago, but I highly doubt they'd come up with Urban Arcana (a D20 Modern setting) or whatever Modern day Urban Fantasy setting anytime soon.
I'm going to disagree on the Mystara thing. Mystara was pretty distinct. You had flying ships (Voyage of the Princess Ark for example) and the idea that the goal of a PC (at the time) was ascension and becoming an Immortal. That, right there, sets the setting pretty far from any stock D&D. If I was going to update Mystara to 5e, Immortal rules would be the way to go.
/snip
Alternatively (and this would be PURE GOLD), they could set it around 800 years before the original in the time when the survivors of the cataclysm were taking hold of the Flanaess (the area of the 'world map everyone knows) and Vecna leads his evil empire from the Keoland Valley whilst the barbarians and civilisations of the time try to oppose his inexorable rise to power.
An Age of Vecna campaign would require the most work, but would be fantastic!
LOVE, LOVE, LOVE this idea. FANFUGGIN'TASTIC. You get the whole Post-Apocalyptic feel, a very dangerous world (Points of Light to use a 4eism), where the PC's are the ones involved in massively shaping the world to come. True, you'd have to eject pretty much all of the lore for the setting since none of the current kingdoms exist, but, WOW, what a great idea.
Please WotC, gimme this. I'd buy this in a heartbeat. Although, looking at the timeline, you might have to go a bit further back. 800 years back, you have the Kingdom of Aerdy become the Great Kingdom which extends all the way to Greyhawk city. Although, this would place it about 200 CY, meaning the start of the Age of Great Sorrows when you have a bunch of Death Knights basically ripping apart the Great Kingdom.
And, this would mean no Castle Greyhawk as well.
