First Day on Planet Earth

Setting agnostic.

The GM plays The Overlord. They have several grandiose aspirations, but can't complete those alone. They created Their Flunkies (the player characters) to assist. Hilariously, these minions know very little, listen poorly, and would do anything to gain their Overlord's approval. 

The Overlord was expecting standardized minions. Instead, each has setting-specific quirks. These should only be corrected if they impede the mission significantly - which a clever rival Flunky could tattletale. An Overlord should use manipulation, bribes, threat or enforced violence to keep their lessers in line. (Similarly, the GM should incentivize being funny, clever, and effective in that order.)

To be lore-accurate: Don't explain the game. Rarely answer questions as GM; answer in character (untrustworthy but consistent per character).

This game is one Quest. The world is crazy magical (or high tech): unintuitive, frustrating and dangerous. Flunkies are seen as contemptible, ignorable or exploitable by outsiders, and that's accurate. Flunkies should be "given" ramshackle/experimental weapons, secret espionage tasks, and bodily changes that make their jobs more complicated and provide blackmail for other Flunkies to exploit. 

Players may always ask what they notice. 
Otherwise, they announce their actions, GM may decide or roll for success (60% chance usually).

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Disclaimer: to run this game effectively, do check in to make sure players are having fun and don't feel like they're getting picked on. The ideal is to have them get mad at the world, not any player or you. If one player is too backstabby they can be given additional responsibilities or punished for hogging the spotlight (ie if they keep calling to complain that their compatriots are suboptimal they could always lose their mouth).

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Setting/Story concepts:

Paranoia: An AI Overlord summons forgettable clones to fix some malfunctioning equipment within its complex. Flunkies get Secret Society missions, R&D explosives, minor super powers, and experimental drugs.
Lich: A to-be Lich is tracking down another cure to mortality. Their skeleton/zombie crew is given cursed weapons, magics, Geases, and more.
PrincessXMaid: A lonely princess served by "maids" needs something exotic to cheer her up. Magic, training, and lust fuel the Flunkies and make them distrustful of outsiders.
Cyberpunk Robo Wrangler: A roboticist hotwires some sexbots to "retrieve" something that "belongs to them." Viruses, glitches, part swapping are all part of the dystopian future.