Well, I'm fairly new to this myself, but this is what has worked for me.
1) Survey your players' skills to see where they fit best as far as position, keeping in mind the offense/defense you want to run. I use a spreadsheet to help me with this.
2) Set your lineup, keeping in mind your training goals. Seems that most people gear training toward improving a few players, while I tend toward training whatever I think will help my team as a whole.
3) Experiment. If it seems like your PG isn't doing so well, give another guy the starting job. Play around, find out who can perform and who cannot. Once you have a good idea who's good and who isn't, start looking on the transfer list to replace the not-so-good players with more useful ones. My suggestion is to go about 1 per week, but whatever you think you can afford.
That's my 3 cents. Hope it helps.