Now that you mention it, though I almost want to run a really decadent Third Imperium "drift" game, Victor's European Vacation in space where they confront the inherent anomie of existence. And do space drugs.
For some reason this really clicks with me. I immediately thought, "Well what if they were all addicts? That would be a pretty dang great reason for them to go adventuring. They'd need money, and that'd get them into the usual trouble, and then the drugs themselves would get them into even more trouble. It'd neatly explain the usual player character batshittery."
Especially if they weren't all the same drugs. Like if I was going to take this concept really seriously, I'd have a random table that told you what drugs you were hooked on at the start of play. Maybe more than one.
It even explains how the characters know each other: You met through your drug dealer. Or otherwise through that fraternity that always seems to exist amongst users and addicts. It'd be easy to integrate new characters into the game. Which would probably be necessary, for something like this.
Traveller is a pretty obvious system/genre for this kinda thing, but I think it'd work for any sufficiently urbanized setting. D&D and cyberpunk would both be pretty obvious options.
I might do it with Traveller, though, just because I've had trouble with that system in the past (for some reason) and that might help me get a handle on the shape of the campaign. Or not. I've been meaning to run a "wastrel noble scions" game of D&D for a while, and this might be just the thing.