When the offense comes to the line the defense immediately begins to dissect the situation and start their adjustments. One of the first things they look at is the strength of the offensive formation. There are some variations to how defenses declare offensive strength, but in general it will account for both running and passing strength. Finding an offense's formation strength helps determine the adjustments. Lets consider a very basic situation:
I did a quick base 4-3 here. Notice Sam (S) is not 3 yards off the ball but rather on the line. That is because the offensive formation strength is to that side (determined in this case by the TE or Y. Of course, that can change based upon where the two backs I did not draw line up.) The DE will stay in his assigned Gap which is outside shoulder of the OT, but the TE creates another running lane so Sam moves to the line to defend the outside run and quite possibly cover the TE if he releases to pass pattern. It depends on the other receivers and the coverage call. Lets just keep it simple and deal with run - the addtional run lane outside Y is now defended by Sam on the line.
But what if:
Since I was determining strength in this case by TE (Y), it is now on the offensive left. To the Defense, this is Will's side. Different defenses deal with this in different ways. One way would be to have Will come to the line like Sam did in the prior formation:
This might well be acceptable if the wide side of the field is still to the offensive right. However, if the wide side of the field is to the offenses left, you might want your best tackler (Sam) on that side. So, you might choose to flip flop Sam and Will.
Neither solution is right or wrong. It just depends on your personnel and philosophies. HS and College have more variation in athletic ability which is to say there may be a huge difference between Sam and Will's capabilities. That athletic difference isn't so prevalent in the NFL and for that (and a few other reasons) you don't see LB's flip sides.
These are basic examples to illustrate the point. It gets a lot more complex especially with the modern passing game. By way of example, consider:
Again, different defenses might classify the offensive strength differently in this case. I would say the run strength is to the offensive right due to Y. However, the passing strength is balanced because you have Twins on the left with X-Z and you have a Twins set on the right with Y-H. The tailback (2) is balanced. How will the defense adjust? Well, it depends on a lot of factors. If its third and long and the DC wants to just stop the big play, he may sit back in a coverage package. Since a 5 yard run would not hurt, he may drop Sam off the line so he can more easily drop into his pass coverage zone. (pass coverage really drives the complexity over run strength).
Okay, I've rambled on too much. Just remember Defensive and Offensive strength are not the same thing. Defensive names like Sam, Will, Mac, Buck are labels for player positions (I could just as easily call them Lenny, Laser, Razer, and Rino). Any defense worth a plug nickle will flex/adapt their formation to meet the offense. Defenses flex or change based on a lot of things such as their own capabilities, offensive strength, knowledge of the opposition, down and distance, defensive philosophy/coaching preference, etc, etc. The run and pass strength of the offense is one factor in determining how the defense will adjust before the snap. (aside: this is why offensive motion into being - it is trying to get the defense to show their coverage based upon how they adapt.)
Hopefully that helped clear up the question of strength.