I was looking at doing this on a PC, and found that an application called "Console" that allowed an easy way to use VST plug-ins in a fairly lightweight host application.  You could, of course, use a more sophistocated DAW application as well.  In my case on a PC, I used the RME's "Loopback" feature to send the Media Player's output back to an RME Input - then Console takes its input from there.  I split the signal into 3 stereo chains, and applied filters and delays (VST Plug-ins of your choice) as needed for L/M/H outputs (each stereo chain goes to a discrete output pair).  On a Mac, Core Audio might allow this w/o using RME's "Loopback" feature, but I dunno.  You'd still need some kind of a host to insert the DSP AFAIK.

There might be a more streamlined way to do this, but I have not seen any pre-baked solutions to allow Loudspeaker Managment and Processing on a computer with a multi-out soundcard (this could be a killer niche software market IMNSHO - basically like a Driverack or even a Lake processor as a "plug-in" or standalone host that would work with any multi-output interface ).

It should work.  If you are on a Mac, you might not even need to use RME's loopback, and use Core Audio to route the channels internally (I'm not familiar with Core Audio or Macs in general, but I believe this is one of its features).  Make sure Reason is properly configured to get inputs 1/2.  I know I had this working on a PC with Console as the host...

You mentioned changing the default settings so that I-tunes will play out differently (different output)? Go into the control panel of your soundcard and change the default playback outputs. Usually, this is either digital toslink, stereo speakers or something of that nature. But it will depend largely on how you have your software crossover setup. If your crossover is set to take its input from the digital output of the computer then you would route the output to your RME's individual outputs going to that corresponding speaker driver. Just make sure they all match up or you could fry some of the drivers.

Essentially, the crossover software may take it's input from the computer digital out. Then the software sends it's output to the RME interface channels.

Try using the digital loopback instead of using channels 1,2. You will then only have one D to A conversion if I am understanding you right.

Hope I didn't make that look too confusing. There are other ways to accomplish this also. That is just one way.

Mikal