Cassandra Syndrome

Really quickly: noisms posted this awesome thing at Monsters and Manuals.  He mentions it with reference to story games, but really you could do it with any sort of game.

Make sure you read it.

Think of how different genres would change the tone: it would likely skew tragic in modern horror games (your mundane life would probably collapse under the strain, leaving you a shattered husk with no allies), but D&D characters would likely become more ruggedly individualistic than normal (nobody listens to you, so what the hell, you're going to do it yourself).

This, of course, assuming that characters don't take advantage of the situation (which seems particularly likely among murderhobos).  Imagine you know an earthquake is going to hit downtown, and will demolish the Lassater Building.  So you short sell the stock and wind up richer than when you started (incidentally, this is what Al Qaeda financiers did with the World Trade Center before it was attacked).  Or it's a fantasy setting, and the characters realize they can steal the Crown Jewels during the chaos caused by the earthquake.

Fun stuff.