What really needs to happen is that Spotlight and Time Machine need to use direct i/o (F_NOCACHE) when they read data from the filesystem, this way they won't pollute the disk cache with their reads and OSX won't swap out a bunch of pages in response.

I think you could probably hack something together that does this with DYLD_INSERT_LIBRARIES (OSX's LD_PRELOAD) that would would hook the open system call and fcntl F_NOCACHE on the file descriptor before it hands it back to the application.