On MFN-2 I had my whole depth chart reset and some players deactivated. Is this possibly happening because I resigned a bunch of players?

You you have more or fewer active players than 46 the AI will reset your active players and thus your depth chart, that should be the only time that happens. Most often what causes this is signing a new player and forgetting to deactivate someone when he's activated, or activating an injured player and forgetting to deactivate someone to make room on his roster.

I hadnt changed anything from the previous game until I noticed the reset, all I did was resign my upcoming FA's.

Is it possible you had an "out" injury that didn't get deactivated?

I did have that, my HB was knocked out for one game literally with a concussion. That may have done it then