Before starting a road trip, make sure you are well rested and have had a decent meal. If you are driving and feeling tired, energy drinks are not the best choice to stay awake. Yes they will keep you awake, but not alert.
Before starting your adventure, make sure you use Google Maps to map out your trip, so you know exactly where you are going. Other mapping software is neither as accurate nor as inclusive as Google, so stick with the best.
If you can, take someone with you that you trust to drive. This way, the two of you can switch driving at preplanned intervals. Also with two people in the car you are far less likely to fall asleep behind the wheel.
Know the law of the cities you will be going through. Some might have outlawed driving and texting or even driving and talking on any device. Rarely does anyone ever get out of tickets with a claim of ignorance.
Make sure you plan to avoid rush hour traffic in major cities. Not only will it increase your drive time, but it will also cause stress and frustration.
If you have to stop or pull over, never do it on the side of the road, pull off into a parking lot. Thousands of people are struck by other motorists every year.
Do not drink alcohol before or during the drive. Not only is it illegal, but it's dangerous.