Before packing anything in your vehicle, remove the clutter that has built up from your daily routine. A stack of mail on the backseat or a hamburger wrapper on the floorboard may be tolerable when driving to work and back, but not when traveling across the country. Your car will inevitably collect more trash as the trip proceeds, so it's best to start with a clean slate. When on the road, regularly dispose of your garbage so the accumulated junk doesn't become a source of stress.
Once your car is cleaned out and you're ready to pack, put some thought into organization. Pack lesser-used luggage, like suitcases, in the trunk or under more frequently accessed items, like snacks and children's toys. This will allow your passengers to retrieve much of what they need without asking you to stop the car. As you get farther down the road, try to stay organized so things don't get sloppier as you go.