When I have a new series starting, the first two things I look at are the starting pitcher for each game for the other team and the park I'm playing at. After that, I checkout the other team's catcher. And depending on these variable, I adjust my lineup accordingly. If I have what I think is a clear advantage in the starting pitching matchup, I might rest a couple of my starting position players and use a couple of AAA in their place. As far as resting players, I rarely play any of my true regulars (including pitchers) at less than 100%, unless its absolutely NECESSARY. I check fatigue on each player before every game, and when their fatigue says overused by 5%, they automatically get a game or two rest, no matter who it is, unless its a crucial or playoff game. Because if you don't manage fatigue properly during the long haul of the season, you'll find yourself with players in the 80's and 90's at the end of the year.