I have several cities and towns on my campaign wiki. Marig in particular is pretty well detailed after having run a half-dozen campaigns in and around it. You can read it to see what I find most useful and interesting...
When I start from scratch, I try to decide the following things, in no particular order:
What is the governing structure of the city and how did it originate? Is the town a nobleman's seat, a free city, based around a port or a defensive site?
Where does their economy come from? Where is the food coming in from? What do they export a lot of, and to whom? What do they import, and from where?
What's the weather, geography and climate, and how does that affect the physical layout and description of the city? Are there sewers? Or are they still using cruder methods of disposal? or magic?
What is the law-and-order structure? do they have police? firemen? paramedics? are they city run, or do people hire their own? Do the guilds organize watches and fire vigils? ARE there guilds?
Magical Medieval Society, as mentioned above, is really good at helping you answer a lot of these questions, in a medieval way.