Try to figure out the group early and tune the game to them. If they just like smashing things (this should be evident if they all have low Charisma scores), try to make a bit more fighting than you would if you see them just getting into character a lot. If you see them acting nuts, don't be afraid to loosen up yourself and crack some in universe jokes. If you really want some insanity and the guys are up for it, limit turn decision time to exactly how long the turn is in combat. I think it was Paranoia that suggested this to me, but if the guy is taking time and saying "Uhhh....", cut in and say "Well [x] spends his turn dumbfounded. [y]?"
Expect the unexpected. Especially if your group is a bit less than sane. They may attempt to kill important characters or take an alternative option. Don't try to railroad them is my advice here...people I know hate it when they get forced into a linear RPG. If they happen to kill THE most important character, just roll with it and try to rewrite on the fly. One game I had my friend killed the "world saving NPC" (Hey, we were in High School and Oblivion just came out. Give us a break), so the DM for that game just made it into a more generic and less "epic" styled game.
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