I wouldn't say we are expert travelers. But we have done it a few times; to Wisconsin, Oregon in the summer and at Christmas countless times, Arizona, Carlsbad, and Las Vegas. Our preference is definitely by car. We are able to set our own schedule, change the schedule when necessary, and take all the stuff we want. We pack snacks and toys and are able to stop whenever the children need to stretch or the baby needs to eat. Its great.
Flying is more of a challenge because you have to haul all the stuff. And with the new flight guidelines passengers need to be at the airport almost 2 hours before the flight. Keeping a child entertained while waiting for the flight and then on the plane is tough. And with the new regulations everything must go through the x-ray machine. Recently on a trip to NY with William I had to wake him up and remove him from his carseat to put it through the machine, the stroller had to go through too. So Not to mention it may interfere with naptime. Bringing a carseat and buying a seat for the child is essential, the child can sleep in the carseat and you don't have to struggle with a squirming child.
A few tips:
buy your diapers (and all other consumables) at your destination
travel during naptime in the hopes that your child will sleep
pack an extra set of clothes for the children and the mom
putting these items in large ziploc bags will help you find things in the bag
snacks and drinks for the kids
new quiet toys and books with few parts to lose
Allow for one hour stop every 2-3 hours, unless you are traveling at night. I keep a shopping list and stop at stores to buy things I have been meaning to get - on our last trip I got hats and mittens for all three kids, new tennis shoes for me, and a few new Christmas books. These items we used on our trip and were small enough to bring home.
We take sleeping bags for our kids. It eliminates the confusion of where the child is going to sleep and the problem with enough beds.
Snacks: low sugar, no mess. Extra ziploc baggies for everything.
We take 2 sippy cups for each child. This allows for cleaning and a cup of milk and water.
Buy bulky items like diapers and wipes at your destination.
We have a DVD player in our car, but only use it when the children are going to lose it. We have found that watching too much tv makes them jittery, so we save it for stretches in the car when we are just about to stop.