You'd better use the restroom!
I make Riley (the only potty-trained child) use the bathroom just before we pull out. Then during the trip drinks are limited. There are times when emergency restroom breaks have to be taken, but for the most part limiting drinks helps with those. Now, they are allowed to drink plenty of liquids. I just don't allow them to sip drinks constantly.
I have Capri Suns for the older kids to drink, and plenty of snacks for everyone. One thing that has made life much easier is fruit pouches. All the kids like them. They usually don't make a mess, and they only cost about $1. When Ella or Nolan get fussy, a pouch will usually get things quiet pretty quickly.
All snacks are within reach and easily accessible from the front passenger seat.
I do not have a TV in my car. I have one iPad that gets passed around and one LeaPad 2 that is shared. I pack a couple bags of toys for the kids to play with when they get bored with technology.
There are also times when I make them put the iPad or LeaPad up. For instance, South Dakota was too pretty for Riley to be absorbed on the iPad. I made her put it up and look out the window. (Isn't that what I did?)
We also sing songs. Pandora has a great toddler station and Kidz Bop station that we listen to. We sing along with the songs and dance. All the kids like this.
A good helper in the backseat!
I am lucky and have a very mature 5-year old helper in the backseat. I realize it is a lot of responsibility for her to take care of a 1 and 2-year old, but she is made that way. She is a great big sister and is very attentive to their needs. She helps pass out snacks and toys. She also lets me know if I need to stop for any kind of emergency, i.e. poo-poo has been smeared all over someone, their clothes, their car seat, and toys. That was fun.
I get on the road and drive!
I do not stop for much. Anytime a state line is crossed I like to get out and get a group photo. Chances are we've been driving for a couple hours and need a break anyway. State lines usually have great photo opportunities and clean restrooms.
Unless a baby in a diaper has poo-pooed, I don't stop to change them. Otherwise, they get changed about every two hours, which is basically the same duration as a nap time.
There are times when I stop. If I need gas, everyone also uses the restroom. Anytime I stop I also reorganize toys, snacks and trash. When I get back on the road I am fully stocked and ready for another 2-3 hour driving stint.
I have my route planned!
Planning road trips is fun for me. I like to research the roads I will be on and any tourist attractions along the way. I study the directions and in addition to my MapQuest app that talks to me, I know which roads I am going to take.
I'm a Choice Hotel member and try to only stay at their hotels. When planning a 2-day driving trip, I look for towns a little over half-way to my destination that have a Choice Hotel. Most of these hotels provide complimentary breakfast which is great when traveling with little ones. My kids wake up and demand to be fed, so it's easy to get on the elevator and go get hot breakfast right in the same hotel.
That's pretty much it. I think anyone can do it.