One thing I've noticed is that very few towns/cities are on true grids. Randolph AFB is an example of where the grids have been 99% followed. This usually happens in the midwest and western US or in planned communities, such as Cape Coral, FL.
On the east coast, there are always buildings that don't sit straight on the road, are offset from the rest etc. They just don't conform to what the rest are doing. The roads themselves generally have been through some changes over the years and have some odd twists, widen in spots or narrow to cross a bridge, twist to conform to a river, things like that. Don't be afraid to do something that looks like it shouldn't be. That's more realistic.