I rarely use the line shift, maybe in goal line situations, just to give the back a little more advantage.
As for reading defenses and QB progressions. The key here is repetition. Learn your playbook in and out. Learn to read defenses. The safeties and corners a lot of times will tip to what type of play formation they are in, man or zone. If they drop into a 4-2-6 for instance you have to know that your deep routes are prob not going to work, focus on a back coming out of the back field or a TE going into the flats. or a crossing route. If they are in man many times you will that the middle of the field will be open, usually a safety will be the only one playing center field there. When you see this you know a post pattern and or crossing patters over the middle is going to be the way to go.
I usually know where I am planning to go with the ball before I snap it based on the defensive reads, and I always have a plan for my hot route in case I read the defense wrong. CB blitzes are the easiest plays to read, if you see a both corners set up on the outside, even if your in a tight formation, you can be pretty sure they might be corner blitzing. You will know as soon as you snap the ball. If you see this hot route one of your outside receivers to run either an out or a short comeback. When the corner blitzes your receiver will be wide open out in the flats. If he doesnt blitz then continue with your game plan and find the receiver you had in mind to begin with.
If they fall back into a 3-3-4, I love to audible to a run play, you can usually get past the 3-4 man rush and get at least 6 or 7 yards before your even touched.
One think I noticed is that the AI for the CPU is much smarter this year, and they make adjustments, they are shifting defensive backs a lot more then I have seen in previous years, and they will blitz from non blitz formations. Pretty tricky!