Simulate it. :)
Naturally I don't mean some highly detailed computer simulation.
I mean sit down with a pen and paper and follow the process through.
Why was it first founded here? What was the purpose of the settlement. Why choose this location. Most settlements are founded for a reason. For example London is where it is because it was the lowest crossing point on the Thames. Other cities grow up around easily defensible areas or other strategic objectives.
Sketch out the early stages of the city. Would they build walls or other structures, how would it grow inside. Take into account natural features that might change the shape of the city, for example important buildings would tend to be on high ground.
What happens? What notable events have happened to the city. Has it been invaded? Grown? Plague? See with each ones what changes it might make to the structure of the city.
As the city expands it grows outside the walls, then more walls form are built around the expansion. Is it remodeled or changed in the process? Where do the people live. Do they grow outwards or upwards?
Think about how each area might change. Where would the rich people move, where would the poor people be able to afford? Would areas decay or be built up. How do goods get in and out of the city, and get transported around, etc.