I have used Hotwire 7 or 8 times for hotel rooms in 5 different states. I planned many of the stops for our honeymoon through Hotwire. I have never experienced any sort of problem with lower quality rooms than I expected or prices higher than what I could have got elsewhere. I was honestly surprised how many people on SiteJabber have had a negative experience. In fact, a few times after booking through Hotwire.com and finding out where I was now staying, I looked for a better price for that same room. I haven't found one yet.
On time my wife was stranded with some friends in Chicago after a plane was delayed. She called me up and had me look up a place to stay close to the airport (before we had smartphones). With just a confirmation code they were able to check in a few minutes later.
I haven't used them for flights, car rentals, or cruises. Given my past experience using Hotwire I wouldn't hesitate at all. My only complaint would be they didn't accept me into their affiliate program so I could get a kickback when I tell my friends about my experience. I guess my blog won't cut it for them. :) Oh well, I still let friends and family know I've had nothing but good experiences after using Hotwire multiple times. As with anything, do your research beforehand; I'm just one opinion.