I've been itching to run a game set in Eberron, using 4th Edition D&D rules. At least initially I'd want to set it in Sharn. My approach to Sharn would be to take its size and population literally, as in this analysis:
https://www.enworld.org/thread...l-ghost-town.111530/
I would concentrate the population into closely knit communities, with a handful of city-sized (25,000 people) communities another handful of "towns" (10,000 people) and an unknown-but-not-enormous number of semi-permanent "villages" (1000 people), spread throughout. Between these regions of relative civilization would be areas claimed by gangs, cults, and infestations of monsters, as well places that have just been forgotten or lost (sometimes on purpose) in the huge volume of the city. In other words, Sharn would be a points-of-light setting inside a points-of-light setting, and ripe for exploration and intrigue and well as plenty of combat.
If things go well, the game could move out into wider Khorvaire and other locales.
There'd be no set campaign, probably just a focus on the PCs moving up in the world by building their reputations and abilities.