Lionhead, the publisher who recently put out Fable III, claims than pre-owned sales on the XBox 360 are hurting sales more than piracy is on the PC. Generally, when you buy a new game from a store, part of the money you give the store goes back to the publisher. But if you buy a pre-owned game, the store gets all of the money.
Lead Fable III combat designer Mike West said,
It's just a depressing situation we're in that people don't think it's worth spending money on computer games. What they're doing is making sure there are fewer games coming out in the future and more people out of work, which is a terrible thing.
The pirates, whatever you do on whatever system, they will crack it. It might take no time... I think the longest it's taken to happen is two days. Someone will crack it somewhere and there's not much you can do about it.
Piracy these days on PC is probably less problematic than second-hand sales on the Xbox. I've been working on PC games for many years and piracy is always a problem. There are a lot of honest people out there as well, and if they like your game they'll buy it.
For us it's probably a no-lose even with piracy as it is. But, as I say, second-hand sales cost us more in the long-run than piracy these days."