Update: I was unfortunately not aware of Shamus Young's severe criticism of Fallout 3 available here to link in the original piece and I regret that. It dovetails rather nicely with what I've written and it's much better executed than my piece. I strongly recommend anyone...
Play the tutorials - otherwise, you'll have no idea what's going on.
Crossing roads can make your drivers confused. Lift them over each other instead.
Check that the catchment areas of your goods stores are actually in useful places.