For the sections that become too familiar I try changing lanes just to break up the monotony. Of course here in the Northeast there is usually some traffic no matter what time of day or night it is, so there is always something to keep the brain focused on the road ahead.
Now the rural stretches with nothing for miles does get a bit challenging. I am currently addicted to caffinated "energy" mints in that situation.
If you are on a dedicated route there are probably other people running the same time that you can watch for and chat with. Nothing will keep your mind on the road like watching for a buddy you are supposed to be crossing paths with.