We are straight through drivers (even when we lived in MD). We buy new cd's for the trip and promise ourselves we won't listen to them until certain points in the drive. When we start feeling tired we pop in a comedy CD (Jeff Foxworthy and Bill Engvall are our favs) and we get to laughing so hard we get "refreshed".
We eat light (snacks mostly). We pit stop in one stop: either a Flying J (gas, bathroom and drinks/snacks) or a gas station next to a fastfood place (gas, bathroom & drink refills/snack at fast food place). Also--the rule is you HAVE to get out of the car even if you don't have to "go" when we stop. Just walking around for 5 - 10 minutes is a nice break.
We also play games: our fav is the geography game: first person names a geographical place (city, town, county, state, country, river, etc.). Next person has to name a geographical spot that starts with the last letter of the previous person's place (i..e I say Maryland--my son names a place that starts with D (Delaware--DH then names a place that starts with E and so on)
We also will stop along the way if something looks interesting to visit (my choice is outlet malls--haha) but you'll see South of the Border (counting the number of SOTB signs is fun---when we used to make the drive down 95 we started with a stash of quarters and whoever spotted a sign first got a quarter!)
While I am not an overly paranoid person, traveling up and down the highways (often alone) I have developed habits:
Just for "safety": I very rarely stop at rest centers (esp. at night). You can't be sure there will be other drivers around and while I haven't heard many horror stories lately when I first got my license many years ago there was a rash of murders/robberies at rest areas. When gasing the car I always use the same credit card/debit card and pay at the pumps (this sounds weird but it does leave a trail of where you have been just in case that's information that may prove helpful if people need to look for you). I also gas up with with my trunk facing the store portion of the station--I don't have a front tag on my car so this increases the odds that people will see my tag coming/going from the store or video surveillance will capture it (although many gas stations have video surveillance--you can't always be sure which ones do). I also always try to park in the middle--so the people in the store can see me--not on the ends--especially when there are many rows of pumps. When stopping at fast food places I always park as close to the door as possible--not in the far reaches of the parking lot. I usually call home or someone where I am travelling to and let them know where I'm at (this also helps if I am alone and tired--talking perks me up--and boy can I talk!).