I've used Priceline for both rental cars and hotels. I've had pretty good luck with them.
A few things you do have to take note of. For hotels, if it's important that you get two beds or some other type of particular room, I wouldn't recommend using Pricelines Name Your Own Price feature. You have absolutely no control over what you get other than a room. And it's been my experience that when you use Priceline and get a really good rate, hotels are less likely to work with you on the type of room. I've had a couple of times that when I checked in they told me the reservation was only good for one bed when I needed two.
For rental cars, for some reason, every time I used Priceline, I ended up in a less than savory part of town in a rental car location that was a little scary. I'm guessing because I got a cheaper rate, the airport locations were not in the mix. Likely because they tend to pay much higher rents and have to charge a lot more fees to their customers because of airport taxes and such.
I've never used them for flights mainly because I wouldn't get a chance to know the times involved. I don't do red-eye flights anymore and it's important to me to leave early in the day and get in at a decent time. That's not likely to happen with Priceline. It's always possible I might get what I wanted, but I was never willing to take the chance with a flight.
So I guess what I'm saying is that if you can be flexible about things, Priceline works fine. If you want some things in particular and they are important to you, I wouldn't recommend it because you never know what you're going to get.