I've done both. Our first cruise, I was a bit afraid to try priceline, so I checked around on sites like hotels.com to find the going discount rate, then ended up booking directly with the hotel. We stayed at one of the Orlando airport Amerisuites for something like $59 or $69. It had breakfast, a pool, and was close to the airport. Clean, but nothing special. Our 2nd cruise, I decided to try priceline. I think I bid 3 star minimum, and we ended up with the Renaissance at the airport for $33 + fees (less than $40 total). Even with having to buy breakfast the next morning, we saved money over our last decision. I've also used Hotwire to get rooms other places and saved a lot too.
Pros/Cons that I've seen:
Booking directly with the hotel: You know where you're staying, what they offer, and how much you'll pay. Downside is it's more expensive (but sometimes
AAA discounts, mousesavers codes or other special offers can make it comparable, so don't rule it out)
Hotwire: you don't know the hotel before you lock, but you do know the price, and the amenities. Usually cheaper than direct, but more than priceline. They offer a sister service where you know the name of the hotel, but it's a slightly higher price. I've forgotten the name, but they usually offer you a direct link from hotwire.
Priceline: You don't know if they'll take your bid. If they don't, you can't re-bid within a set amount of time (problem if your trip is coming soon!). They describe "typical" amenities at that level of hotel, but don't guarantee that your hotel will have them (can be an issue if you need a shuttle or a free breakfast). Pros, usually the cheapest price around.
It really depends on your personal preference. Hope this helps! Lisa