I have played other football games, and this one is a bit harder to get used to.
Here are some tips that might help.
Try to stop running with your quarterback before you throw. They can throw a lot more accurately when they are stopped. This is hard sometimes because the defense is trying to tackle you, but it is the best way to get an accurate pass. If you keep getting tackled before you pass. Try starting off in a shotgun position. (Where your quarterback starts a bit back from the center aka. the one who hikes the ball)
If there are no receivers open, press the Z button, and you can run with your quarterback.
A juke is best used when you are in the open field. If you are running up the middle, it just takes up time. You want to move forward, not side to side.
It is better to start off on first down with a short/medium pass, or a run. The long passes are best for third down and long or second and short. (Second and short is a good time for a long pass, becasue if you miss, you can use a short run on third to get the first down.)
On third down, if you have more than about 4 yards to go, it is best to use a pass play. (Keep this in mind on defense too. You don't usually want to call a run defense play on third down if the computer has a long way to go.)
You should probably punt on fourth down if you haven't made it past midfield. (Again keep this in mind on defense. You will want to call a special teams play on fourth down if the computer has a long way to go. Usually a punt block or a punt return)
Kicking a field goal is very tough if you have not made it past the 40 yard line of your opponent. (When the numbers start going down, after you pass the 50)
Using the Z button before the play on offense and defense is very useful.
-On offense, if you are doing a pass play, it shows you where your receivers are going to run. This way you can get a look at where the defenders are, and where the receivers are going to end up. If a receiver is on one side with only one guy covering him, he may be a good choice to pass to. But, you always have to see what happens after the play starts, and who is open. You never know what the defense is going to do.
-On offense, if you are doing a running play, it will show an arrow where the guy is going to run. If there are a bunch of defenders in that area, you may want to call an audible, do a line shift, of call a timeout and call another play. (Don't worry about those too much at first. Just play without them until you get pretty good)
-On defense, there will either be an circle lit up, or a line pointing from your player to an offensive player. When there is an area lit up, this means you are in zone defense. You should try to stay in the area that is lit up, and watch for receivers coming into that area. If they run out of that area, don't worry about them. There may be another receiver coming that you need to cover. If there is a line pointing from your player to an offensive player, that means you are in man coverage. You should cover that guy the entire time.
-I usually use a linebacker.(The guys in the center of the field.) Or a lineman(the guys that are right on the line of scrimmage)
It may be best for you to sort your plays by type, instead of formation. This will make it easier to call plays. You may want to learn the formations eventually though.
Hope some of that helps. It is a simple game on the surface, but is actually very complex.