The mystical secret history genre (think Tim Powers) is ripe for roleplaying. Unknown Armies sits squarely in this space, and many modern-setting games are compatible. They work because people largely share a sense of history and historical importance. If I say “the lost survivor of the Titanic” or “the sketchbook of Aquinas” or “the last words of Eva Braun,” there is a social and historical context that gives these things meaning… and the potential for power.
In a homebrewed fantasy setting, this sort of thing is difficult. Players won’t have the established knowledge to make such things meaningful to them. Telling them facts or expecting them to read up on histories you’ve written is unlikely to be effective. This can be accomplished more effectively if the characters care about the historical facts in question. I need to think about how to do this most effectively.
Still, this is one of the best uses I can think of for long-established campaign settings. With the right group of players, running a campaign around secret histories set in Greyhawk or the Forgotten Realms or Tekumel… or even Middle Earth… would be simple… and could be incredibly compelling.
Thinking about it, there are a lot of classic D&D adventures that could really be recast in this light – many of them are centered around ancient tombs of historically-important individuals. Reworking them might largely be a matter of tone and objective.