We like to have a car at the beginning of our trip, since we stop for groceries and then do some non-disney activities. Then we drop it off in the Anaheim area and take a taxi back to the airport. We don't like the hasle of dropping off the car at the airport, and it's much easier to have a taxi drop us off. Since you're a family of 6, you will need to rent a mini van, so you're probably better off taking a shuttle or taxi. If you do decide to rent a car for the first part of your trip, you can pick up from the Alamo at the airport and drop it off at their location in DTD. Budget will work as well, as they have a location on S. Harbor. I don't know if Great Wolf Lodge charges for parking, though, so you might want to look into that before making your decision.
A previous poster mentioned having a car for medical emergencies - we had a medical emergency once when we didn't have a rental car, and we took a taxi to the emergency room. Much better than driving ourselves, since we wouldn't know where to go or how to get back!