Many here are missing my point.
I am not talking about the inherent advantages of the triple option itself (that the QB can occupy tacklers with those options rather than blockers.)
For example, I am talking about lining up to make it seem you have a numbers advantage on one side to bait the TO to run to that side. Then, you overwhelm that side from the snap. That is certainly "easier said than done" and requires a defense with players fast enough to close the ground given up by lining up to confuse the offense.
You would still have to execute to stop the play, but the defense would have a numbers advantage when the QB was assuming a numbers advantage for the offense.
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More defensive player perspective on trying to stunt/slant and/or appear to overplay one side:
First, thanks for a fun and reasonable question that has produced some good discussion during a slow period on the boards....Can't wait for Spring!
What you are describing, where a player on the DL lines up in one position with one apparent responsibility, but then moves on the snap to another area with a different responsibility is generally called a stunt, slant, or twist, depending on how he gets there and/or the coordinator's terminology.
Several things conspire to make this an unwise approach to defending PJ's offense. First, as you noted, the spread makes it difficult to get to a different area quickly to discharge your responsibility because you have farther to go.
Second, the BASE triple option plays are quick hitting. The B back does not line up deep and read where to go. He lines up close to the QB and explodes on the snap to a pre-ordained spot. The first option hits the defense VERY quickly. There had better be a defender there, or else the B back gets the ball and is off to the races. So, if you are stunting, there is a good chance the B back may end up right where the stunting DL just vacated OR the B back blows through an area your stunting DL may not get to in time (particularly if he gets chipped by an OL on the stunt). If either happens, you have a big 230+ bound monster rumbling through your defense with fast OL moving quickly to the second and third levels of your defense. That can take the spirit out of a defense pretty quickly.
As far as overloading one side and forcing the offense to run in one direction, that would be crippling yourself. The offense would take that deal every time. Why? The TO is a downhill running attack run out of a balanced spread formation. Even against balanced defenses it uses motion and speedy play development to generate favorable numbers playside. The two slots are speed/space that are rapidly deployed to take advantage of numbers. Thus PJs offense can very quickly exploit numbers if a defense lines up unbalanced to begin with. There would be no way to get over quickly enough to cover fast plays to the undermanned side. Even if you could, PJ will read that like a book and make you play by feinting to take your bait, then countering the other way.
What I see as a wise defensive strategy would be to have a few BALANCED defensive shifts that the defensive front can hop in and out of prior to the snap (after the offensive line has made its initial reads). Having a few different balanced alignments that you move in or out of prior to the snap will create uncertainty in the OL & make OL and QB reads infinitely more difficult. These multiple pre-snap alignments would also make it hard for the offense to snap on the first sound, as they'll have something different to look at/think about each time they line up. Perhaps some snaps later in the game don't shift at all, an maybe catch a lazy OL who is waiting for the shift to make his read.
The danger would be confusing your own guys and making them think too much. Defenses play best when they can just line up and react. If one of your guys gets out of position, there is a big play liability against a fast, well-disciplined team running a downhill option attack out of the spread.
Best defense is just to play physical and disciplined.
Just some more thoughts.