My most used campaign setting is a homebrew world I call Sheth. My first real hand at GMing was for this old 90's D&D clone called Darkurthe Legends, which included its own campaign setting in the rule book. When I returned to gaming in January '14, I reflected on that system and setting as I prepared Sheth for a D&D 4e table. 5e came out 9 months later, so I adapted the setting to the new system, a sort of Sheth 2.0.
It's undergone additional revisions over the years. 3.0 changed the cosmology and timeline to make the existence of the gods uncertain, and to transform demihumans from god-made creatures to products of natural evolution. Still a high fantasy setting, just not with all the stock fantasy assumptions. The next few revisions were pretty minor, but added a lot of lore as I continued to flesh out specific areas of the world through game play and the contributions of players from previous campaigns.
Including the 4e version, I've started a total of 7 campaigns in this world, but 3 of them ended prematurely so I usually only say I've run 4 campaigns in it.
The only other setting I've run was when I DMd AL Expeditions season 1-3, which would be Faerun, Moonsea region.