What great courses have seen major changes in their routings (not including switching front and back nines)?
Merion is the first one that jumps to mind in the U.S. Hugh Wilson's original routing hit over Ardmore Avenue on the 2nd, 10th, 11th, and 12th holes. When auto traffic started to get busy, the club bought the ground for today's 11th green and 12th tee, and William Flynn re-routed holes 1-2-10-11-12-13 to fix the problems.
In the U.K. routing changes were much more common: Muirfield, Royal County Down, Royal Dornoch, and Ballybunion were all changed drastically from their original routings, some more than once, before they arrived at the routing that made them famous. It was easier to do because of two factors:
1) The open links terrain makes it much easier to re-route than on tree-lined U.S. courses; and
2) The Brits are not so precious about who designed their courses, since many of them were initially laid out before golf architecture was seen as a profession.
Also, as Peter alludes, on some sites the ability to shape and create is more important than routing, because there aren't so many features to take advantage of.