BigJoe- I would say the biggest thing is make sure you have people who want to play the game. If someone even questions whether or not they want to play turn them away. There is nothing worse than having players who give up or volunteer to be voted out.
Really really work on the challenges. Go through every possible outcome and come up with a solution for any problem that might happen. It took me a few seasons to get the hang of this but I have it almost perfected. I spend about 5 hours working on every challenge I do. Some more depending on the complication of it.
Along with that plan out the entire game. Always have the idea in your head that anything that could go wrong will go wrong and have a plan of action to fix it. I make sure that every challenge can work with different numbers of people. For example if one team wins every challenge, eventually you might have to do a game with it being only 2 vs 2 where as if the wins are even it will be 4 vs 4. Have the entire game planned out with extra time in case something goes longer than expected.
Also make sure you are passionate about it and enjoying it. If you don't have a passion to make it awesome it's going to suck. If you really put your entire heart and soul into the planning it will come out amazing. I have eight seasons worth of material I would be happy to share and help give ideas!
