Sure can.Really, you can run a whole campaign in a big city.
Though it can be nice to contrast it, too. The 5E game I've been running is set principally in a great, ancient grey city full of stone tower blocks and weird baroque nobles and goings-on. The starting PCs were all younger scions. But their first initiatory quest into full adulthood took them into the Feywild, which IMC is more like a traditional D&D fairy tale world, albeit with humans few and their villages scattered. Most of the campaign has been split between this two highly contrasting settings, via a gate the nobles have access to.
BTW, I want to express my compliments on your choice of handle and avatar. That cover art is the same as the copy of the book I've had since I was a kid, and man was I affected by that story. So good.