This is what I've done, and I'm not the best GM in the game but I usually make the playoffs:
1) Set your game plan 'matrix'. You only have to do this once, and then adjust it from time to time. Offensively, figure out what you want to do on 1st dn, 2nd dn, etc, and plug it in, either graphically or by text. Just set what you want the identity of your team. Defensively, it's a challenge. I used the 'secondary' tab to pick plays where I wanted them, but you can use the 'linebacker' tab too, there is no right or wrong way to do it.
2) I check my playbook usually at the beginning of the season, again halfway through the season, and before the playoffs. I take out plays that aren't working (based on avg per play) and put in plays that might work better.
3) Before each game, I check my depth chart, then pick the plays I want scouted. Lastly, I go to the run/pass ratio, (under defense) and adjust the ratios based on what my opponents is running, which is listed below the sliders. I always pick 100% run or pass, dependant on the majority of my opponents play choices.
That's pretty much all I do...