Gauss' suggestion of the "Boxer Rebellion" strikes me as the best one. I can imagine something like Freedom Fighters meets Sid Meier's Pirates!, where you gather a small resistance around a procedurally generated period Shanghai as the foreign powers seek to strengthen their hold -- and then at the final, climactic attack to rid China once and for all of the corrupting foreign influence, their rifles raised high against you and your unarmed comrades...
Your fists start glowing. The roar of a Celestial Dragon. A smile. And so you begin the wholesale, as-mandated-by-heaven slaughter of the British.
... and then you blink. And the British are still there. And they fire. And you all die.
The Zoot Suit Riots / The Bracero Program as modern-day commentary on NAFTA and the drug trade in Mexico. Set in an alternate future Elizabethan kind of Los Angeles. Narrative is a loose adaptation of Shakespeare's "The Tempest" and "Othello." Everyone speaks in Elizabethan mannerisms but with Latino slang intact. Can't think of a gameplay mechanic yet. Whatever happens, it culminates in the Riots and everyone dies -- the impact the riots have, however, is the result of the player's agency.
You are Lech Walesa trying to organize and maintain the Solidarity movement against the USSR in 1980.
Other undeveloped ideas / historical events:
- Colonize Australia.
- Darwin in the Galapagos; hidden object game meets Pokemon, except not the stupidity that's Pokemon Snap.
- 1979 Iranian Revolution (which apparently surprised a lot of people at the time?)
- West / East Berlin; you're a boy trying to convince another boy on the other side of the wall to try to escape across -- at the end, the twist is that the boy dies trying to cross from West to East Berlin.
- Stonewall Riots; a squad RTS where you command drag queens and transvestites against the police.
- Chinese annexation of Tibet.