I have flown back and forth across the United States a couple of times and will probably take an Alaskan trip this summer.
I plan for three hour legs, even though the planes I have flown all had much longer ranges. I am 51, and the bladder doesn't hold out as long as the fuel. Sitting too long also is a good way to give your passengers and yourself some serious leg cramps. Plus, I don't want to get sleepy.
General advice on long cross countries like these:
1) Always take extra food and water. A snack on the plane can relieve the tedium and help keep you alert. Also, you never know when you are going to show up at some airport after everything is closed and you haven't had anything to eat.
2) Take a cell phone. Second best is a phone card. You need to be able to call taxis and hotels, and if you get in after 7 at night at a lot of airports the phones may be inside locked terminals.
3) Take the AOPA guide or another guide that lists hotels, taxis, rental car companies, etc.
4) If you are going on a weekend, make sure that your fuel stops will be open. If you want a rental car, reserve one in advance. You would be surprised at how many airports are closed on weekends. Many rental car companies are also closed on weekends. Enterprise, for example, does no business between Saturday noon and Monday morning in most areas.
5) Always use flight following. Having ATC to talk to can keep you from going to sleep.
6) I don't care what time of year it is, always keep some warm clothes on the plane.
7) Don't eat at MacDonald's. I don't have anything against MacDonald's, but it seems a pity to fly 1000 miles just to eat the same thing I could get at home. Similarly, there is surprisingly little variation between the interior of one bar and any other. Get out and see the neighborhood.
8) Carry the maintenance manual for your airplane, if you have one, windshield cleaner, extra oil and a funnel, extra hydraulic fluid for the gear, and a small tool kit that includes a tire pressure gauge, screwdrivers, adjustable wrenches, a spark plug socket, a safety wire tool, one of those long grippy thingies that picks up small objects in deep recesses, a dental mirror, needle nose pliers, jumper cables, duct tape, WD-40, disposable rubber gloves and plenty of rags. It would not hurt to bring a set of tiedown ropes and chocks, too. Do NOT forget the tow bar.
9) Carry light sticks. I can say from personal experience that it can get awfully dark when the cockpit lights go out, and flashlights just don't cut it. You will also need at least a 2 D cell flashlight for ground operations. The aforementioned cell phone will invariably be found wedged under a rear seat, especially if it is after dark and it is raining and cold.
10) Always plan at least one extra day for every three weekdays and for every two weekend days you think you will need. Things break and weather goes bad. Usually at 6:30PM on Fridays. The second most popular time for things to break is at 12:30PM on Saturdays -- right after the rental car companies close.
11) Don't go to Houston during the National Rodeo Championships unless you really enjoy 4 hour waits for taxis, being charged double the usual rate for a hotel room you wouldn't keep your dog in, endless wais at restaurants, etc. Same goes for anywhere within 50 miles of Anaheim for the opening of Disney California and similar region-buster events. (I got trapped by these particular events -- on the same trip!!!; discovering others is left as an exercise for the student.)
12) Take a copilot. I have yet to fly anywhere that I enjoyed visiting when I was just by myself. And it is nice to have someone who can handle some of the workload both in the air and on the ground.
13) Make sure that everything you take with you fits in a single bag that meets airline carry-on requirements. Don't be afraid to abandon the plane if necessary to continue the trip. Paying for a commercial flight and/or a ferry pilot sure beats sitting around an airport for a week or two while the plane is repaired or the weather clears.
14) Always make sure you have adequate cash to pay cab fares and to tip the drivers of courtesy vans, baggage handlers, waiters, etc. This can easily run $50 a day. Tips and cab fares are just about the only things you need cash for, though, unless you insist on eating at MacDonald's. Note: even if a cab company advertises it takes credit cards, odds are the driver will give you grief if you try to pay with one. A credit card will handle the rest.
15) Don't count on being able to pick up charts, approach plates, publications, etc., at interim stops. The few airports that actually have pilot shops are almost always out of what you need.
16) Did I mention to not forget the @#$! tow bar?