I used to ingore these people but now I have more fun thinking of creative things to say:
1) Appropriate for use when driver is in an SUV, "Wow, your car is big. Your penis/boobs must be pretty small."
2) "I'm sorry you're out of shape."
3) Confuse the hell out of them by pointing at another car and saying, "People like _that_ take the fun out of flossing."
4) "Why don't you come back and we'll find out who works out more. Where are you going?"