1.) Get a decent hotel relatively close to the CC and walk there, traffic will suck so don't plan on driving around it much.
2.) The early games are often less intense due to the hour, I like to schedule myself for the lectures and discussion panels for this time.
3.) Evening games are often vibrant and heavily booked so register for your slots months in advance if you can.
4.) Many new items or books make their debut at Gen-Con and often ahead of announcement so bring enough money in case something catches your eye and you can't walk away without it.
5.) Eat lunch and dinner at off-hours if you can, or you'll spend more time than you want standing in line.
6.) Get to know the people playing and running games, get email addresses and IM info, this year's co-players are next years friends to watch for.
7.) Todd Rooks runs seriously great games in the free-style listing so watch for his stuff and join in.

Hope this helps ya.

-- Nathan