Inspect the Room First
If you have a baby or small child, be sure to quickly give the room a once-over. You'd be surprised at the things that are left under a bed and that you'd never want your child to play with. Also, if you have very small children, you may want to consider baby-proofing the room. Pack a kit with a few outlet covers, table-corner covers, tape, rubber bands, etc.
Be Organized and Set Up Stations
Have one of the adults take the kids exploring while the other gets everything set up.
Nothing is worse than needing to change an explosive poopy diaper and having to dig through a suitcase to find diapers, wipes, diaper cream, etc. So, upon arrival, get yourself organized. Set up a feeding and diapering station so you have a go-to spot, just like at home.
And put a sheet on the floor with toys if you've got an upright baby or crawler.
Be Flexible with Routines
The importance of this one cannot be stressed enough! If you try to stick to a rigid sleep schedule, you are going to be setting yourself up for a lot of frustration. Plus, your toddler can sense when you are stressed. Sure, keep to it loosely, but keep in mind that this is a new place to sleep, and it's simply not going to be as easy as it is at home.
Book a Suite
Obviously, this is not always an option financially, but if you can book a suite or even two connecting rooms, then do it. The extra square footage is huge when trying to squeeze a family into one room. If you can't, then ask at check-in if they can upgrade you. Sometimes they will and sometimes they won't, but it certainly doesn't hurt to ask.
Keep it Clean
Hotel rooms are small, and fitting family in there, with all their stuff, can really get chaotic if you don't keep on top of the mess. Keeping your room clean will cut down on frustration, big-time. If you drove, you can even stow empty suitcases in your car to alleviate some clutter. And don't forget, stepping on Legos in the middle of the night in a hotel room doesn't hurt any less.
Latch the Door
Always latch the door. Children, for whatever reason, are fascinated with hotel-room doors, and because you can't really lock yourself or your kids in them, you can latch the top to ensure that your kiddos stay put. This is especially important if you're sharing connecting rooms or a suite and not always in the same room as your tot.
Bring Sleep Aids
Hotel rooms are full of weird noises from the outside hall and surrounding rooms, and they can also be quite dark at night. Toting along a white-noise machine and/or a night light will do wonders in making your child, and therefore you, get a better night's sleep.
Have Something to Do After the Kids Fall Asleep
If you're going to be sharing a room with your child and you don't especially feel like going to sleep at 8 p.m., then bring a book with a light or your iPad so that you you can entertain yourself without waking the kiddos.
Bring Easy Entertainment
A child without things to play with or read is a child who is going to drive you nuts in a hotel room. Be sure to show up with a few go-to things to keep them busy and don't forget that there is always the TV if you need a few minutes to get yourself ready for the day.
Most importantly - HAVE FUN!!