When our son is on the road heading to our house or his in-laws, he loves the challenge of using Priceline for booking his night's stay. Thank goodness his family is adventuresome because they pull into the parking lot and go online on his smartphone to book. They have gotten some great deals and some not so great. Bob and I, on the other hand, are not quite so adventurous when it comes time to where we are going to put our heads to rest for the night.
If you are a plan-ahead type one of the best ways to assure a good room is to join the chain's loyalty program. When you book on their website and use your loyalty card you usually get a better choice of rooms. One article I read said that the Priceline and other low price sites to book through get the "ice machine" rooms or basically whatever is left. With our booking we have even been able a couple of times to choose our own room. Of course that's not always best if you don't know what side the freeway is on. Just sayin'.
If you have any special requests or concerns, you can always call before arriving to be sure your room is what you expect. For example the king size bed rather than two doubles and certainly a smoking/non-smoking preference.
Use a credit card rather than debit or cash. You have a lot more recourse if you are wrongly charged for something. Besides, the right credit card can earn you points toward more travel.
Double, make that triple check that you have the right hotel in the right place when you are booking online. For that matter make sure you have the correct date as well. We booked the wrong night once and arrived to find we did not have a room reserved until the next night. Luckily there was a room available but it had us scurrying to check the rest of our reservations for that trip.
And probably something I should have started with is to check reviews and compare prices of different hotels in the same area. Reviews are especially important. Those online pictures may show some wonderful amenities and property views but the tale is told best in the reviews you can find online at places like TripAdvisor.
While booking on the fly night by night might be a great adventure, I prefer to know where I'm getting my Zzzzzs ahead of time.