Well I guess the exterior would be in for an overhaul to match the layout, unless you were meaning the unexplained mysteries of the end of the hall and some of the doorways leading to rooms.
Obviously, all inside rooms of the Tanner House could not fit in the house that was used for the exterior shots. I'd say that if the Tanner house actually existed, it would have the same exterior design features, but would be proportionally larger to accomodate all the rooms that are on the show.
The unexplained mysteries of the end of the hall have partly to do with there only being one entrance to the set. The hallway set probbably starts at the front of the stage, and goes back to the wall at the end of the stage. Thus, both the living room stairs and the kitchen stairs lead up to the same spot on the second floor. We have to suspend disbelief and believe this is actually two different points, even though the doorways would be in different places if viewed from the other end of the hallway. They also have the same doors leading to different upstairs rooms at different times, and I've never bothered to figure the ins and outs of that.
The other problems are that
1) The hallway doesn't have enough doors
2) I'm not sure the hallway is balanced in terms of how much length would be required for the rooms on each side
3) I'm not sure it's even consistent which rooms are on the same side (though it may be)
4) The hallway would have to be longer than the space between the living room and kitchen stairs
5) The door to the attic is not part of the hallway set (I've not seen it, at any rate)
There'd definitely have to be some choices made about second floor for it to be in proportion with the first floor, and this would likely involve getting rid of 1 or 2 rooms (the room that was Michelle's and then DJ's room, and/or the room that was Jesse and then Joey's room.