My wife and myself are planning to travel with her sister and husband this comming fall. Last fall we made the Grand Canyon, Sedona, Vegas trip and had a great time. We're looking for some ideas for this comming fall. We'd prefer a fly-drive trip, don't mind the driving and like to be able to stop and move "off route" if something interests us.

I think you might have answered your own question when you said "something that interests us"...Do the four of you share any particular hobbies? - wine, foodies, hiking, antiques, history. You can focus and taylor any trip around your favorite interests. Last year I organized a trip just for knitters www.stitchawaytours.com
So pick your favorite things to do and go for it!