Using opaques without at least a cursory investigation of what transparent channels are providing is like chucking money down a Porta-Pottie.
It's not surprising that naive users have made Priceline's hotel operation ridiculously profitable. People think half off "retail" is a good rate for a hotel (think about the Entertainment! card discounts, half-off promos from FF programs, etc), and PL's "retail" pricing has been shown to be widely inflated (there's discussion here and at other bidding strategy sites). The messaging and marketing by Priceline is downright misleading (the infamous messages that your bid is far too low to possibly be accepted, so how's about raising that $10, huh?). People get caught up in the heat of bidding and keep raising. They bid too soon...there's just a zillion variables.
That said, I've spent a lot of time on this (literally dozens of stays totalling hundreds of room-nights), and I save a lot of money using PL - there's a property I stay at regularly where I get a PL rate of $32 and the negotiated corporate rates for a few major companies nearby are $109. The lowest non-opaque rate I see for this property is usually $89.
I use Hotwire when I can't get PL availability, and as a last resort, I go to other channels. But, with a bidding strategy, some recon, and an elementary knowledge of how PL accepts bids and hotels manage inventory, I honestly cannot see how an informed user can't beat direct booking or Orbitz/Travelocity/et al by at *least* 35% off their lowest displayed price, even taking into account booking fees (note that since taxes are a function of room rate, in some high-tax areas, the difference in tax between a PL bulk rate and a published rate that is only $20 higher can more than make up for the PL-assessed "booking fee", even on a single-night stay).
Eric