This summer, my husband and I packed up the car with our 4-year-old and 2 month-old (with my parents along for the ride in their car as well) and headed out for a 5,000-mile road trip from Southern California to South Dakota and many stops in between. We have been taking our oldest daughter on road trips every summer since she was 2 months old, so by now, we feel we have it dialed in pretty well as far as planning goes. Kids will always keep you on your toes, so there are always things to learn no matter how well you think you have it set up. When we tell friends we take our kids on these trips every year, I always hear "we could never do that!" and I am here to tell you, yes you can! It is all about a mix of novelty and consistency to keep it interesting but also familiar.
Planning for the Trip
Plan for stops. You will just have frustrated kids and parents if you don't allow for breaks from the car along the way. We planned to stop about every 2-3 hours since that is how often the little one eats (still nursing), plus that's about the time everyone needs to use the restroom again. If you know that is built into your travel time, then you have a realistic expectation of how long it will take and not just the time Maps tells you it will take. Driving early in the morning was always more successful for us than trying to leave around noon.
Packing the car
Snacks, snacks, snacks.... I think any mom of a toddler will tell you they love snacks for every meal and all times in between. Individually wrapped snacks are the easiest in the car (think bags of goldfish crackers, veggie straws, trail mix, dried fruits, fruit snacks, graham crackers, etc.) so buy bulk (Sam's Club or Costco) and put them in individual bags or buy the snack-sized packs. I took her with me shopping so she could pick out some special treats I don't usually buy for the house to make it fun and something for her to look forward to. Trader Joe's is my favorite place for this since they have so many choices in small-ish packages. We also packed a cooler with apples (she eats apples almost every day and that helped keep life somewhat consistent away from the house), Cuties tangerines, almond milk for cereal (her usual morning choice, again keeping with the consistency as much as possible), and energy drinks/coffee for the adults because let's face it, parenting is tiring.
We also purchased a car seat tray for the road trip when my daughter was 2, and it was the best thing EVER! She can eat on it, play with little toys and not have them fall on the floor, use it to prop up her tablet, or draw/color on it. We always pack a small bag of toys and books for her, coloring book and a pencil pouch with some crayons (twistables are the best!), and a tablet. Now that she is a little older, we had the bag next to her so she could reach in and get what she wanted. When she was younger, we would switch out what she had at stops to keep her entertained. I also go to Target Dollar Spot before and get a few new things she doesn't know about to bring a little excitement when she's starting to get bored.
Picking Stops along the Way
We have found that oftentimes, rest stops are the best place to get out and stretch our legs and use the restroom. They are (generally) clean and often have either a playground or grass area for the kids to play on. While we were stopped, we also took the baby out of the car seat to make sure she had time to stretch out as well. She loved the opportunity to lay out and get some air, and would be enough of a break from her seat that she was able to go another 3-ish hours in the car. McDonald's was also our go-to stop since they are everywhere, have Wi-Fi, delicious iced coffee, and generally clean bathrooms. The bonus was a new toy to play with in the car from the happy meals. 
Finding a place to stay
If you are staying in a hotel, staying on the bottom level was always easiest for us. Then you don't have to haul all the luggage upstairs, and if the kids are jumping/running around you don't have to worry about people underneath you. We also found a few cabins along the way, and one had a bunk bed. It was one of the coolest parts of the trip for my daughter, she talked about it the whole way. Sleeping in new places can be a challenge, so we brought kids melatonin for our 4-year-old for the nights she was having trouble sleeping (mostly because she was too excited from the day). For the baby, we brought a co-sleeper bed for her and also had a portable bed.
The Fun Stuff
Most of our trip this time was sight seeing, which might sound like little ones wouldn't do well, but she loved it! We bought her a pair of binoculars, and that helped her be more interested in what we were looking at since it made it more of a novelty looking out of those rather than just looking out the window. If you are going to National Parks, make sure to visit the Junior Ranger station at the Visitor Center, they will give them an activity book tailored to their age, and a Junior Ranger badge. My daughter was begging us to go to more places so she could get another badge and book. Point out animals you see along the way, no matter how many deer we saw, she was still excited to see wildlife on the side of the road. If time allows, stop at a park along the way. Sometimes when we would stop for meals or gas we would see a local park and stop for a few minutes to let her get some energy out. We would set a timer so there wasn't a fight when it was time to leave, she knew when the timer went off it was time to go. There are often free things to see along the way that are fun things to stop and see (think Cabazon Dinosaurs) that are a fun little break to get out for a minute and see. 
I hope these tips will help you have a wonderful trip! Enjoy the ride, and take it as it comes. There will be bumps along the way but have realistic expectations. Don't expect everything to be perfect, because it WON'T be, but you will get valuable time with your family and make memories to cherish forever... even the hiccups make for great memories!
