Offensive players are such simple creatures of habit, and as a result their individual moves and team structures can be figured out simply by watching them for long enough. And they're selfish, too. And lazy. And they cry when they break a fingernail.
This is most obvious off a called play, especially one where each player's motions are choreographed. If your man isn't a featured cutter, there's an excellent chance that he won't be cutting hard (selfish and lazy). As soon as you see him sorta but not really cut, you know that a set play is going to the place just vacated. And the thrower is afraid of incurring the wrath of the play creator (who is probably the coach or captain who is in charge of subbing), so he's going to throw it because "it's the play". Poach block, give and go for the goal, boo-yah.
Even if there is just a four-man string called, if your guy is cowering on the sideline or just mingling with the other sheep, he's not in the play. If he is alert and separating himself from potential picks, well, at least he's not an idiot, but he's live, so get up there in his face. (Just a secret between us defenders: hack the shit out of him early and often. So what if he calls a foul because you grabbed his arm as he was running by you? It stops the flow, right?) And take note whether he lines up in one part of the stack when he's in the play and another when he's not.
But your savvy and attention to detail will really pay off during the flow. Some self-proclaimed smart guys will claim that they take what you give them, but they are so used to playing against stupid defenders that a smart defender will be able to set them up. (Well, it's not so much we're stupid as we're egotistical. "Ooh, I'm so fast, I'm just going to run by him." But simple physics shows that just a half second head start will usually be too much to overcome. Try this experiment during your next track workout. Take the 2nd fastest and 2nd slowest players and have them race. Give the slow guy a one yard head start, and let him start whenever he wants, with the fast guy reacting. The over/under on when the fast guy will catch him is 40 yards.) Make him think that he can just run straight after a token fake, but you will already be moving in that direction, with your excellent positioning preventing him from going the other direction.
But you don't have to "set up" the cutter in order to play good defense. Just know his habits. So-and-so always fakes for the dump and cuts up the line. Whats-his-name jukes at you and cuts in. blah-blah fakes in and sprints straight deep. It's not a fake if you know what he's doing.
And this applies to marking even more. Learn what he does to break the mark, or if one fake always leads to a particular throw.
No matter how good you are, you're still going to lose 4 out of 5 confrontations. Just try to minimize your losses in those 4 and make that occasional victory a big one.