Wow. I wrote more than I meant to. Sorry.
TL;DR: Comfy clothes. Ambien. Long layover = maybe go to a lounge.
Not so much now, but I used to travel a lot. Both for work and fun. My longest one-way trip took over 60 hours: 4 planes and 2 helicopters. A lot of my time was spent in layover hell.
Plan ahead with your clothing: comfort and layers are your friends. Jeans, belts, and restrictive clothes are the enemies. Take off your shoes and throw on a pair of warm socks. The floor can be COLD sometimes. Airplane blankets are shit. You're way better off with a comfy fleece or sweatshirt.
Some carry-on suggestions: extra clothes (at minimum: extra tshirt, socks and underwear). All charger cords and adapters. deodorant, toothpaste, toothbrush.
Bring your own headphones and some tunes. Or some audiobooks. Some people really like those noise canceling headphones, but I find some good earbuds do the trick for me. You can generally plug them into the in-flight entertainment too. You might grab one of those airplane adapters, just in case. I haven't run into that plug style lately, but it's probably still out there. Don't fall asleep listening to in-flight entertainment, unless you want to get ear-fucked by the next announcement at full volume.
The death of happiness is the neck crick. Maybe find a good travel pillow? Try some out ahead of time, so you're not finding out that it sucks after you board. I've had zero luck here, so I just take some ibuprofen and suffer.
Once you're all warm and snuggled up against the sweaty fat guy next to you, and you're listening to some tunes, here's what you do: take two shots and an ambien. Time travel achievement: unlocked.
Layovers. ARG I HATE LAYOVERS. It's not so much the long flights that get me. It's the long layovers. I can handle 14 hours on a plane, but even a 3 hour layover makes me want to die. Lounges can be a lifesaver, if you have some extra money. LPT: find reviews for the lounge before you pony up the cash! Some lounges have lots of space, showers, booze, and snacks. Others are crowded shitholes (I'm looking at YOU, Delta ATL B lounge). Some lounges may have a dress code, but I've never had an issue. Just don't look homeless and it's probably fine.
In closing, good luck! I love to travel, but those long transits generally suck no matter what.