Do you have a level range in mind? Some things like a sewer crawl may be better for levels 1-5 rather than a 12th level adventure. Also, how large the city is? Waterdeep can have anything, where a smaller city may be more of a town to some people.
My problem with cities is that they are more abstract in dealing with people and places. I am not mapping all of Waterdeep and listing all the people and places. I just assume that there is about anything the PCs need or want to get. I try to have several NPCs available and a few groups of bad guys to interact with, but the size of a city can be daunting.
I like to have a mystery in a city. There may be an item people are looking for and one of the other gang has it. Trick is that the other gang is setting up the first to take the fall.
A grander idea is that the city is under attack. Depending on how much you want to plan and work at it. Also a city may have big defenses already for a attack by orcs or giants.