The arch-villains of the world (or across a large section of the world) come together in a "Legion of Doom" kind of situation to take over the world. Reaching into/across international and interracial politics, trade, religions, magic, etc... Kind of like where the Slavers series was trying to get do, but on a much larger scale.
Some might be NPCs the party faces at lower levels or they will get to know/face individually before the big organization is all revealed.
Despite being thwarted at several turns [presumably] as the party grows in power/experience, the BigBads succeed (in large measure, again, presumably while the heroes are chasing some red herring or taking care of some side quest) before the party gets to level 10 (or thereabouts). Then [at the more "superhero" levels] the game switches to taking them down/restoring what Good remains in the world.
EDIT PS: Oh yeah! Also, in my campaign world, humanity was first created as "the Five Tribes", each of which was devoted to one of the Elder Gods (now, mostly dead/gone) and identified by the colored glaze that was used/assigned to each: the White, Black, Red, Green, and Gold tribes of Men. One of them excelled in knowledge, wisdom, and beauty above the rest. The tribe of Gold, who was assigned/adopted by the elder god of knowledge/history/the mind (one of the few that still exists within the current pantheon), utterly disappears from the world's historical record centuries ago...there are no accounts, hardly even fable or myth, as to what became of them.
I've always wanted to do a "the Tribe of Gold [or "Golden Men"] Returns" but never have ...yet.