I have to drive for a living, some 50-60k miles a year. I reach my limits at different points. There have been several times where I have had enough, I will stop right where I am and get a hotel room for the night. I use a variety of techniques to avoid total burn-out; take alternate routes, stop and browse thrift stores, etc. I usually carry a small folder with me, when I get where I am going I can get some riding in. My nemesis is Washington, DC. I will drive over an hour out of my way to avoid that mess. My normal travel route is pretty much from Philadelphia, PA to Jacksonville, FL along the I-95 corridor. Fortunately there are several alternate routes. My biggest frustration is the lack of caring or ability of drivers to control themselves and their vehicles.
Aaron