When I start work on a custom city I first choose the settlement model that is the best size for the city I want to build, and has enough room for the buildings I want to include. I've tried very hard to avoid a number of the very 'circuitous' settlement models that RTW included...namely, settlement models where the path to the plaza is\was very long and twisted around. The large and huge city models were guilty of this, and I've used them sparingly.
I have also tried, where possible, to make roads inside settlements wider by placing buildings further back from them where I could. This allows units to march better in their natural formations, and can avoid some of the 'crowding' when going around corners. I'm not saying that is always the case, but it is something I keep an eye on. I also test the path-finding in every town\city by actually fighting battles..and\or watching the units walk around the city in the Strat map city view. I can actually more easily spot problems in the city view.
Now, obviously, some settlements are going to have issues 'by definition'. Hilltop, fortress-type cities like Pergamon that use the original celtic hillfort model are going to be challenging. There are only two paths to the plaza, and the ways are narrow. But these settlements are also smaller and meant to be difficult to conquer. So I guess the main idea is to provide a large variety of different types of settlements that will look and feel different. So far, I have probably built in excess of 45-50 settlements.