If you need a car when you arrive, there are six car rental agencies in both Terminal 1 and Terminal 2. If you have a car waiting for you, be sure it's in the same Terminal where you land. Most overseas flights from the USA land at Terminal 2. If you have to go from one terminal to the other, use the Sky Line shuttle on Level 4 leaving every two to three minutes.
When setting off from the Airport, follow the blue Autobahn signs or the yellow signs for the B43 highway. Take the Autobahn A3 going east toward the Frankfurter Kreuz. The Frankfurter Kreuz is the cloverleaf for A3 and A5. Follow the A3 bound for Wurzburg. Get off the Autobahn at the Aschaffenburg West exit.
Here is a link to car rentals at the Frankfurt Airport: http://www.bnm.com/frank.htm
