Imagine you are working for some video game company. What would you do to frustrate the people who are too cheap to buy a legal copy of your game? Some games, like Earthbound, just freeze at important events and eliminate all your save data. Spyro 3:Year of the Dragon actually tells you that it knows it is illegal.
So, here are my ideas:
All characters (friends or foes) will attack you (like zombies).
very cruel loading times.
instant death from falling a few feet.
the visible layer is offset from the physical layer (walk on water, drown on land.
no water at all (walk under water glitch.)