Watching Harold and Kumar Go to White Castle got me thinking about comedic duos and a game about them. And about untapped markets for rpgs (like pot smoking hippies) and genres for rpgs that don't involve magic or sci fi elements. So why not an rpg about two slacker kids getting into hijinks, a la the above movie, Cheech and Chong, Jay and Silent Bob Strike Back and several movies I haven't seen?
I think you could have a game that only has two players (maybe one GM and two players) who are defined by their similarities and differences to each other. The characters in the game start out on opposite ends of player defined spectrums: Bob is silent, Jay won't shut up. Harold is too focused on his work, Kumar is too irresponsible. Felix is neat, tidy, and neurotic, whereas Oscar is slovenly and casual. Ernie is mischievous, Bert very serious. Don Quixote has his head in the clouds, Sancho Panza down to earth. In many instances, one is fat and the other thin. Over the course of the game, the characters move around on the spectrums (some or all of them) which has various mechanical effects.
And then there's the pot hijinks, which probably works off of the sliding spectrums. I'm not sure how, exactly, though. Perhaps being in a given place on a spectrum has advantages and disavantages. Sometimes you want to roll higher than a trait, sometimes lower. The other player can introduce off the wall complications to a situation. Possibly the drug itself is some resource, though I think I prefer it as a character goal pursued by one or both PCs or possibly left out altogether for just a Comedy Duo rpg.