Every spring and fall Dad would drive 1,000 miles straight through. He had it down to a science, hitting the major cities early in the morning when traffic was almost nonexistent. He did this into his late eighties.
I help the youngest son move 2,500 miles driving a U-haul truck pulling their car on a flat bed trailer. Unfortunately he had a 4 hour window we had to hit at the far end which limited our traffic avoidance options. We made the window with a hour to spare by driving straight through the night before. I was glad when that trip was over.