Prepare Your Car

Get an oil change.
Check your tires, coolant, wiper fluid, etc.
Clean out the interior of your car so you have a fresh space.
Make sure you have your insurance and registration documents in your glove compartment.

Things to Pack

Freeze some water bottles and place them in a Yeti cooler. They will stay cold for a really long time and will also act as ice packs for any perishable food. Stash the cooler on the floor between your back seats. Hotels usually have ice machines, so you can refill your cooler with ice along the way.
Healthy snacks that do not need to be kept cold like apples & nut butter, granola bars/protein bars, nuts & seeds, beef jerky, popcorn, and dark chocolate.
Paper towels, wet wipes, and disinfectant wipes.
A medical first aid kit & car kit for emergencies, including a flashlight, jumper cable, and a spare key.
Cash in case you cross any unexpected tolls or pass a roadside farm stand that is just too tempting to ignore.
A pillow and blanket for the passengers.
Electronic cords like USB cables, iPad cables, and camera cords. A car inverter can be ready handy for charging multiple items at once.
I imagine this seat organizer would be very helpful for those in the back seat, particularly if you have children.
Use a plastic cereal container as a no-spill trash can. Place a plastic bag inside the container and put the lid on.
Use a shower caddy or a laundry bin to keep loose items organized in the trunk of your car.

Wear comfy, loose fitting clothes & shoes that are easy to slide on and off.
Check out the Roadtrippers app to help plan your route & find places to stop.
I use the apps Waze & Google Maps to navigate, but you can still find good old paper maps at some gas stations and tourism centers. Download offline maps on Google Maps, so even if you lose service you can still find your way.
Embrace the local food scene and incorporate unique foodie stops into your journey. Ask the locals, look out for regional magazines, or search blogs ahead of time online. Diners, Drive-Ins & Dives is a fun resource for laidback spots approved by Guy Fieri.
Listen to long music playlists, podcasts, and audiobooks to help pass time.
If you did not pre-book your accommodations, use the Hotel Tonight app for last minute hotel reservations.
I like to save my favorite discoveries during road trips on Google Maps so I can reference it in the future.