Charge enough for the game before you make it that you won't lose money if all the copies after you make it are pirated. That's the very best way to handle piracy. As a bonus for this strategy, you can make sure people who pre-paid get something nifty (but preferably not gameplay unbalancing) for their faith in you before you even had a product.
Barring that, just ignore it. If you can't make enough money on the game, tell people that you weren't able to make enough money to pay for your time and are thinking of leaving the business. Give figures on how much you made (not on what percent you think was pirated) so people can see that you made squat on making something decent and useful for them.
If you want to, you can try offering people who can prove they don't have a pirated copy stuff that isn't necessary to play the game, but is nifty and shows off that they bought it. This works especially well if your game has a strong online component. This works even better if there's some sort of way to allow people to purchase this item in-game for the cost of the game.
Charge for access to the server if it's an online game.
Set it up so players are solving some random problem for you by playing the game. Make money selling that solution.
Stop trying to force people to give you money. Trust in them to give you money if you make something good enough. People know how it works. And a gentle education is usually all that's needed if they forget.