My friend is currently running one. I would recommend reading Pokemon Adventures or at least the summaries for a good story. I wouldn't mess with the future too much and let encounters of Pokemon stay random. Starters should be chosen within reason not just pick from three. A recommend new region over future. Keep Pokeballs easily available. Have sheets for players, not just their pokemon. Team rocket is a good default enemy with clear cut goals that will avoid a "Im a bard don't kill us" situation. Make leveling easy nothing sucks more than five long campaigns and no evolution and also have as much info prepared ahead of time. You shouldn't need a rival or a babysitter. The players will be their own rivals and the Professor will point them in the right direction. Even though I recommend a new region I would pick and choose from current Gym Leaders and Elite four. Players love to see familiar faces. Kill Pokemon. If it falls -10 it is dead. Allow creative battleing if it is table top I don't want turn base. If you need a NPC don't use one with Pokemon. Final piece of advice is to avoid paradox Pokemon with a mystery. Shedninja will kill if you look at its back, Diglett cant be scene, Slowpoke Pokedex says it evoles with Shelder. Your players will want to explore but don't let them ask questions you don't want to answer.

Thanks for the advice. I have made all new gym leaders and a whole new crime team. I am writing it that the players pick a goal for them selfs like pokemon master, gym leader, doctor, breeder, etc. for evolving i was going to do it more like the anime and manga where the pokemon evolve when they are ready to but they still gain levels. the starters were going to be the 3 from the first 3 gens and the players will have skills like handle pokemon and when they get a new pokemon it would be if they can control it or not and other skills as well. But there are going to be 12 gyms they can battle but only need 6 badges to compete if they want to in the legue. again thanks if you have any other tips tell me i am open for new ideas and i will give you credit

70 year old Red...OH THE HORROR YOU'VE UNLEASHED UPON THIS WORLD!

The best part is I have him still alive and 'retired' he has his full team from Gen 2 but they are 10 lvls higher minus pikachu he is 100 and a badass.