with scheduled time outs like IRL and some turnovers = out of bounds etc to more closely emulate real game play and create more opportunities for substituting players to alleviate fatigue issues

Great idea

also make it so that over time play does not incur fatigue (or otherwise recalibrate the way players are substituted in OT)

I echo these suggestions wholeheartedly

co-sign all of this

I disagree about overtime.  Overtime minutes IRL make people as tired as non-overtime minutes, and if your team gets too fatigued to play overtime games, then you haven't taken enough minutes.

but in WIS OT you dont have any control of the substitution in that limited amount of time (5 minutes) and in real life guys who average 5 minutes per game don't fall over from exhaustion if they happen to play 20 every now and again

real life is not a good comparison in this matter - the issue is WiS fatigue and substitution protocols which have no real life cognates

The depth chart gets flat out ignored when overtime or foul trouble hits.  You have no control over who plays the minutes, and sometimes it does really weird stuff like putting someone who's 85% effective at a position when there's someone who is 100% available to fill it.

so basically fix OT issues or if you can't at least don't penalize because of it

I've even tried putting more than 48 minutes in at a position in case of situations like this arise.  For example, I had 07-08 Manu Ginobili, 08-09 Danny Granger & (I don't remember year) Vince Carter.  That was almost exactly 96 minutes a game between the three of them.  But I could never get them on the same page.  So I started putting Vince in at 36 minutes (starting at the 3), Ginobili in at 31 minutes (starting at the 2) and Granger in for 36 to 44 minutes, backing both up with several surplus minutes.  Reason being - the "empty the bench" rule & foul trouble.  I figured Granger would get extra minutes when the other two got in foul trouble or it came to mop up duty, but no, I had Nocioni and Joe Dumars coming in (without being on the DC at all) in both of those situations.  I also tried this in another league with less than satisfactory results.

I've also had problems with starting a guy playing less minutes than his backup.  For example, I had 1645 minute Donyell Marshall starting and 2131 minute Chuck Person backing him up.  Well, I could put Marshall at 14 minutes a game and he might play 20 or 24 or 28, while Person (whom I put anywhere from 26 to 34) would play really random minutes.  I found that when my PF or C got in foul trouble, it was putting Marshall over there and taking a scrub in instead of putting Person in for more minutes.

I also had the same problem with 1499 minute Dennis Scott and 2021 minute Dale Ellis.  I couldn't make Ellis play enough minutes while Scott played too many, no matter what I did (unless I started Ellis).  Was really frustrating.

Also had issues with 1996 minute Allan Houston and 2312 minute Michael Redd... Wanted to start Houston and have Redd come off the bench and back up both the 2 & the 3... yet I never could get Redd to play enough (while Houston had continual fatigue issues).  I eventually gave up and started Redd... everything worked fine at that point.

Another situation... 94-95 theme league... I had Stockton starting at point, Kidd at SG, Barkley at SF with Majerle backing up Kidd & Barkley, Kidd sliding over to backup Stockton.  Majerle consistently had trouble fulfilling his full minutes, while Kidd had too many (Barkley, too).  I was relieved about Kidd, actually, since he was playing back-up, too, but again - I had to take extreme measures to get the most out of them (extreme being changing my starting line-up occasionally to get more minutes from Majerle and less from Kidd).

These are just a few examples.  I almost always have a platoon of some kind on my teams, and the only way to avoid this is to drastically underdraft minutes (which is a bad option in a draft league or theme league with no rookies, because then everybody gets tired).

So there's some real substitution issues at play when it comes to putting big minute guys on your bench.