This is more for when you have your own truck and can "free drive", but the GPS isn't just used for getting from one job to another. You can plot pretty much anything on the game's map by dropping pins. Want to drive from the dealership in LA to a rest stop in Vegas? Drop the pins in the menu map and let your GPS show you the way. This is also great to do when you're trying to get to towns you haven't discovered yet.
If you miss your freeway exit or get lost somehow, don't fear—the GPS will automatically redirect you and find you an alternate route. Also, If you get in a bad accident or can't get "unstuck" from a ditch, call assistance services. It'll cost a fee and take some time out of your job, but they will drive you to a nearby town and you can get your truck fixed, or just continue on with your journey. I don't recommend doing this during quick jobs, though, unless absolutely necessary.
Much like driving in real life, it pays to be aware of your surroundings in the game. Some of the highway exits (particularly in Arizona) are a bit confusing so be sure to check your map for your turns in advance. Also beware for things on the road like sudden traffic, accidents, road work, and road closures. All of these random events can impact your journey as well. Don't worry about tumbleweeds, though. Unlike real life, you can run over them without messing up your tires!
Check out your GPS while driving- if you're in an area you've never been before, you'll see all the roads are grey, but as you drive down them ("discover" them), they'll turn yellow. You can see the same roads on the menu map. This is a great tip for completionists who want to reach 100% coverage in the game!