Thanks for the response, everything you said sounds reasonable to me. I've been catching on to the importance of the separation of 'real-life' football and this game, which has been pretty interesting. I get that player talent is by far the biggest factor and that it is often better to pick a formation based off the talent that will be playing in that formation instead of based on any particular matchup. Since I can't do anything about my player's skills overnight, I like to focus a lot of thought into game planning or at least understanding the game engine better.
In this case, I am hoping to understand the significance of me, say, running a heavier-than-normal pass offense against someone who only plays a 4-3. I'm hoping to understand why me running the ball out of trips has been so much more successful than running the ball out of pro in this game when he plays a 4-3 against both (both are set to 75% outside). I want to know how I beat what is probably a heavy blitz defense with what I have now (aka, more checkdowns to my RB, shorter passes in general, runs to the outside?). I totally get that player ratings is the significant factor here, but I also think there are clear effects of the play calling in effect here, such as me getting sacked way more than normal despite having played against other teams with comparable LBs and DLs and me completing a lot more big passes despite his corners being much better than teams I've completed less passes against. A lot of this will be trial and error on my end, but it's always helpful to consult the experts here that have been doing this for years.