Jeez where to start...
We did a 6 month, 16 state, 6000 mile trip after retirement and learned a lot from that trip. We are in the middle of a 3 month trip now, so the first thing we learned from our retirement trip was that 6 months was too long :)
We've shortened our travel days to 4 hours planned (5 hours actual) and our stays from a week to 2 or 3 days (3 days if we're someplace interesting). We also are staying at more state parks than private parks in an effort to keep the costs down. We do Harvest Host when we can and plan to do some boondocking on BLM land when we get further west.
We do the interstates only when absolutely necessary and prefer to travel on the old US routes as a rule (we're doing US 2 now) and try to avoid narrow, twisting roads through mountains.
The retirement trip, we rented a car when we needed to get stuff. We rented from Enterprise (because they "pick you up") but we found that the pickup distance is a certain radius from an office and we were picking campgrounds based on proximity to an Enterprise office - not the best criteria. Also we found that some Enterprise locations are merely an office in an auto body shop and there's not always an Enterprise employee there when you drop off to check the car for damage and release your liability.
This trip we're towing an Equinox. Towing is much better because you can just go see stuff. Towing is just one more thing to worry about whereas renting introduced about a dozen things.
Driving 10 miles off route to save 10 cents on a gallon of fuel is lunacy. It's better to pick a station that is logistically friendly. Pilots and Flying Js are easy in and out but they're expensive and the diesel lanes are disgusting. Gas Buddy and Google maps street view are your friends for finding a station that you can into and out of easily.
The best advise I can give is don't over-think it. Planning every stop down to the minute is worthless. Nothing ruins an adventure like having to be somewhere at a certain time. If there are friends and family along the way that you want to see, pick a date to be there and work backwards. In spite of what you hear about crowded campgrounds, you don't have to have reservations for every stop before you start off. We normally know where we're going next stop and are working on a place to stay after that, so we're only reserving a week in advance. Of course, this won't work for popular campgrounds at the height of the season. This worked fine for us in central into northern Florida.