1) Take a break every two hours!
Did you know this? The mind tends to wander, "Highway fever" can start to take over, you easily lose attention span, and that's how accidents can occur. To reduce this risk it's recommended you take an out of car break to stretch your legs and get fresh air once every two hours. It sounds like a waste of time, but it saves time compared to what you'd spend if an accident were to occur!
2) Sleep during the day
If you're taking a multiple day/night trip make sure when you're resting and sleeping that it's during the day! Studies show that while less places are open at night and that is a disadvantage, that the roads are also much less occupied. Driving at night can mean less waits in traffic jams and less risk of a car to car collision.
3) You may not need a break... but your car does.
Even if you're car is brand new, fluids are topped, and tires are new... extended driving without stopping can have a MAJOR impact on the future condition of your car. Constant stopping heats rotors, constant driving has tire wear, and prolonged engine heat can lead to stretched belts... so even if you don't need to stop, stop every few hours for your cars sake.