Another thing to think about is that all the extra time that someone plays at "getting tired" is in a degraded status as compared to 'fairly fresh'.
I personally almost always set my starters to 'fairly fresh', and my backups to 'getting tired', unless I have something really non-standard going on (like, I have only 5 or 6 players that are good at all, etc).
You might ask, why getting tired for backups. Well, when the starters are ready to come back in, they do .. regardless of the setting of the backups. If a starter comes out and is ready to return, if the backup is at Fresh, he still comes out for the starter.
So, the backups generally will not get tired anyway .. unless someone fouls out or something like that. In that case, I would likely have one of the backups play longer than someone not on the depth chart come in out of position.