You'll need to make up lineups against Left-Handers and Right-Handers. Remember that all players have a VsL rating which shows how much better/worse they do against left handed pitchers.

Over the course of the season you'll have to give players days off... if they have played for long stretches without a day off there temporary ratings can decline... also plan on having injuries and write to the commisioner what you would like see happen if any of the starters get injured.