There are differences in the two offenses and when defending against them with my 3-4 defense I have to make significant adjustments to account for those differences. The way that I try to understand it is to imagine that I am looking down over the field from a bird's eye view. I believe that the calculations that take place in the game engine formula that give us the results of a play are not conducted instantly but in steps. These steps are in effect timed intervals, I just use one-second intervals to keep it simple. At the beginning of the play the offense lines up in a formation, and the defensive players are then aligned by the game engine to that formation and the depth of the pass defenders is set according to the settings in the defensive playbook. So as you look down on the field and watch the players begin to move, freeze it every second while the game engine goes through its calculation and moves the pieces (Players) on the game board (Field). Think about the data that must be inputted into the formula to make this work, you have the attributes of the players that are matching up head to head, you have their experience level, their fatigue level etc. But a huge factor is the distance between the players at the beginning of the play, as the play develops defenders must close that distance in order to get involved in a play. So the beginning distance and the speed of the players involved matters. Now from your view above the field examine the difference in the beginning distances for the receivers and blockers between an I-Formation and a Pro-Set offense. You should now be able to see how both the coverage on the field and the blocking on running plays will change between the two offenses, it also changes which players on defense will have the time to cross the field and get involved in a given play.
I have often advised coaches that if they wanted to use multiple offenses I suggest Pro-Set, I-Formation and NDB as the only viable options because of roster limitations. What phimutau is doing has the potential for a lot of success, especially if he can figure out how to use the advantages from each formation to exploit the inherent weaknesses in every defense.