My mother, in addition to being a lady who lunches, is a frequent traveler. My parents, both retired, travel at the very least 4 times a year. Here's what she's taught me and the girls.
It starts with picking up 2 gallon ziploc bags (or, another brand). And yes, I know those aren't the best for the environment, but for these purposes, completely re-usable. Plus, I'm pretty sure you can buy biodegradable ones at Whole Foods/Trader Joe's.
Figure out how many outfits you need, and then pack everything (socks, underwear, pants, shirts, etc.) for that outfit in one bag. Folded nice and sucked of all air, it should all fit just fine except for sweaters and the like, which can be rolled to prevent wrinkling and save space.
My mother has traveled enough that she's built up her own supply of travel-size shampoos and other toiletries. Take those samples and you're set for your next trip that's not in a hotel! I'm also a big fan of taking the pens, too. Throw them in your purse, where you're most likely to next be searching for a pen.(Also, a nice memento to have around that just might make you smile unexpectedly.)
If your kids are younger, use this same philosophy of packing for them. If they're older, they will have so much fun doing this themselves! I don't think I've ever seen my girls tackle a chore with so much enthusiasm. I just had them show me each outfit before we packed them.
Since everyone's bags look alike these days, add a colored ribbon to make yours stand out on the baggage carousel. Or go ahead and let the kids get decorative with their stickers and patches.
Get something different for the kids to do on the road/on the plane than their usual. I've found some great age-appropriate travel activity books on Amazon. And save another new activity for the ride home.
Try not to have too many surprises on the trip. My girls love to know the itinerary from what time we're leaving for the airport to what they'll be doing each day of the trip, and what time they get to go home. No matter how great a trip is, we are always ready to go home at the end of it. And don't overpack that schedule. The adrenaline, the newness will wear off. Even though my kids are too old for naps, we would all get exhausted in the afternoon during our NY trip, and spent about two hours in our hotel room between daytime and nighttime activities; one hour to veg, one hour to get ready for the next thing.
If you're a single parent, don't let all the "real families" scare you. While I've certainly had those moments, I finally realized, hey, I'm doing something that take most people two adults to carry off! I've also really enjoyed traveling with my parents. Not just for the help, but we'll often enjoy a glass of wine at the end of a travel night and talk, and that's really nice, too. When I'm alone, I'll have the wine, curl up with a book and revel in not having housework to do at the end of the day!
Finally, keep expectations in check. I can guarantee that not everything will go perfectly. Elevators will break, a meal will be disappointing, and of course, flights will be delayed. Don't let it ruin the trip for you. Find the humor in the situation and the smiles, laughter, and joy will follow.