@Banzai, are you using the default lineups UI, or 7-day lineups? The latter will override AI choices for seven days, so you get exactly the starting lineup (and pitchers) you want on each day – but after those 7 days are up, I’m not sure what happens.
In this Perfect format, unless you’re going to check your team every 3-1/2 hours, it’s safer to use the default lineups. Make sure to fill out the lineup for both LHP+DH and RHP+DH.
You may already know this, but also pay attention to the backup/utility slots in the bottom-middle of the screen, because the AI by default rotates utility players in (to rest starters). E.g., your star LF may be set to start, but his backup may be playing every 3rd game. It’s usually good enough to play the utility backup only “when starter tired.” The exception might be a high-stress position like catcher, where guys can get very tired after 3-4 games. I also do set defensive substitutions for weak fielders – usually just 1 or 2 at most, though. You can get a visual look at your lineups and subs by looking at the graphical depth chart.
The depth-chart system is designed as much for injuries as fatigue, so isn’t quite as important in PT as in regular OOTP (where injuries happen quite often, as in real life). But it’s still important here.
If you already knew all this, I apologize for over-explaining!