The printed design has remained the same but the form factor has been pretty static for the last century or so. Things like bill readers are a big reason for that once they appeared it became a lot harder to swap around bill shapes.
I remember hearing that the Susan B Anthony dollar coin failed because there was no extra position in the coin drawer of cash registers to put it in. Can you image if every cash drawer now has to be redesigned to have different sized bills?
(I know, I know, it's not actually that big a deal. The drawers have removable inserts, but you get the point of it.)
(actually, on second though, automatic bill readers in vending machines, etc. would need a big retrofitting, that's probably much more a big deal).
The cash register issue I think could be papered over by just having the bills be smaller than the existing bills, ie $100s stay the same size and we cut off a bit of the bill for each denomination step downwards. That would keep them fitting in the drawer and be in line with the pattern of other countries who also make larger denominations physically larger.
