One workaround you can do is to add lots of symlinks to keep the old paths working. This is what they do in Gobolinux (a Linux distro that has a radically different filesystem organization)
One funny thing about Gobolinux is that you could still do the equivalent of a / /usr split.
You never really search /Programs for binaries, you aim that at /System/Index (housing the equivalent of the classic FHS for compatibility reasons). This means that things do not really need to live in /Programs to be useful.
And because of that you have two tools DetachProgram and AttachProgram that allow you to place a package (really just a tar-ball of the /programs branch) in an arbitrary location and have them be symlinked into place.
Thing about Gobolinux is that it do not depend on special Gobo only features. Everything is built around tools you will find in any *nix, and any action can be performed manually if need be.
Nor does it demand that something upstream do something special to placate them, as long as --prefix or similar actually works.
