1) Try to arrive Wednesday afternoon. Hotels have check-ins around 3pm so earlier than that isn't very useful. Use this time to pick up your badge and tickets if you went for will call because the line, as long as it might be, will be considerably longer on Thursday morning. The main hall opens at 10am; get to the doors around 9:30~9:45am to be able to see/hear the opening die roll.
2) Plan with room in your budget. Cons are full of amazing things: be prepared to have something irresistable pop-up on you. I recommend fifty to seventy dollars of wiggle room, minimum.
3) Plan around food and water. DO NOT TRY TO GO ALL DAY WITHOUT A MEAL! Your experience will suffer if you jump from large meal to large meal. Try to eat two meals a day and snack when possible. Do not eat the food in the conventional hall itself. The stuff isn't very good and you'll be eating in a massive crowd with, likely, few places to sit or focus on your food. To this end...
4) Go to the CVS. If you go north from the northeast corner of the convention center it's about five or six blocks to a CVS were you can buy reasonably priced water, soda, and basic food items. Buy something portable (granola bars; fruit; gummy snacks; etc.) and keep some on your person. Also, while there...
5) Buy handsanitizer. Humans are disgusting creatures and if you go into the convention hall anything you can touch will have been touched by hundreds or thousands of other people. I recommend cleansing your hands whenever you leave the main hall and wash with soap and water before eating food.
6) Don't buy too fast. Books are heavy, as are dice and other small items if you start piling them on. Consider spacial concerns before making purchases. Some stands have new items arrive over the course of the con, usually on Saturday when the big day visitor crowds are likely to be so new stuff can come in.
7) Look up. Look up to see the massive numbered banners, which allow you to naviagte the huge dealer room.
Look down. Carpets aren't always even and a fair number of children can be found at GenCon. Be careful of where you are going.
9) DO NOT STOP IN THE MIDDLE OF A LANE! The passages between the booths are quite broad but can be quickly narrowed by people stopping. Likewise, don't stand in the center of crossroads. Whenever possible step into a demo area or use exposed cement spaces at the corners of crossroads to step off of the road and allow traffic to continue on. If you stop at a display, try to present as thin a profile as you can. Stand as far to the edge of the road as you can and turn sideways against the "current". If you have a backpack, remove it and set it beside you to present it protruding into the lane.
10) If you are lost or confused, look for individuals with staff badges. They will do their best to help you.
11) Have a contact who's been there before. I am perfectly happy to give information and assistance to other GenCon-ers, especially RPPR listeners. Provided it doesn't disrupt the RPPR Meet-Up or the games I'm running I will be happy to go out of my way to provide assistance.