I only read the OP so forgive me if anything I'm saying has already been said. This is simply our experience and reasons for traveling the way we do.
Our rule of thumb is that if we can make the drive in a day then we drive. If it were a drive that we would need to stop and spend the night then we fly. It has more to do with comfort than economics.
It is a 16 hr drive to my in-laws in Colorado, and about 16 hrs up to Cedar Point in Ohio. We drove, but we haven't gone since the twins were born (they will be 3 next week).
The longest drive they've been on is from here to WDW which is a 12-14 hr drive for us depending on traffic flow. It takes 14 hrs if we get stalled for construction or an accident. We live close to I-10 and we take nearly the entire trip. We take 10 until we get to I-75 to head south to Orlando.
Our girls travel really well. All my kids have actually been really good travelers - my oldest dd is 15 now. Our mini-van has the entertainment package, and they watch movies the whole way. They do get restless so that is our cue to find a McDonald's or Burger King with a playground so they can burn some energy. Fifteen to twenty minutes of playing and they are ready to ride again. To get them back in the car, we tell them that Mickey and Snow White are waiting for us and we have to hurry because they want to see them. Works like a charm.
Our driving schedule looks like this:
Leave the house at about 4:30 AM
Make Baton Rouge, LA before morning rush hour traffic that kicks in around 7 AM
Stop about 30 minutes outside Baton Rouge and get something to eat. Let the girls walk with me to the restroom to change diapers and stretch their legs.
Drive until 11:30 or 12, we're usually inside Florida by this time. Find a fast food mentioned above to let the girls play. Diaper change. We eat our lunch while they play and take their lunch with us to let them eat in the car while we continue on our journey.
Around 3, they get restless again. Stop at playground and fill the gas tank.
Drive until we get to I-75, turn south. Stop at rest area, let girls stretch their legs and we all use the restroom.
We roll into Orlando around 6 - 6:30.
When we go in May, I don't know what it will be like since the girls are potty training. I'm expecting lots more potty stops.