My answer is, "It depends."
It depends on you - do you enjoy driving? Do you find it relaxing? Or is driving a necessary evil? Do you have experience driving long distances in a day (~500-600 miles)? Did you enjoy it? Do you look forward to it? Or are you a stressed, tense, white-knuckle driver?
I'm a salesman, and seasoned road warrior. I love being behind the wheel. For me, the journey is a big part of the fun. Plus, my wife and kids are great road warriors - nobody gets carsick, and they'll read a stack of books. They grew up taking long trips, so they're used to it. We have a DVD player, but never use it.
In 2011 we went from Michigan to Yellowstone for our vacation. Racked up 5500 miles in 18 days. Longest drive was 614 miles in a day, from MI to Rochester, MN. I did all the driving, and loved it. Also had several days where we covered 500 miles. This summer, we're driving to the Grand Canyon - 2036 miles. We'll do it in three days. I'm actually throwing around the idea to try to make it to Albuquerque in two days - 1630 miles.
On the way back, we'll make some shorter drives.
When the kids were younger, we did the Disneyworld vacation every year. SOP was a 3 AM departure, arriving in Atlanta the first night - 700 miles.
If you're tense when you're driving, it can be very fatiguing. But if you're relaxed and enjoying it, go for it!