Actually this will work quite well. I have a similar setup with my Mac Pro Server. I'm running two x5650 instead of higher clocks since its only a server and not actually being used for anything other than my media for my family/friends and myself. The dual x5650 Xenon will also save a little on power costs in the long run for me as well. I have plex setup on it and my family and friends stream from it everyday even though they are now across the county since i moved from CA to FL. I guess it's a good thing that i have a 1gb fiber connection lol.
I'm running 6 3TB WD red drives (similar to your 4tb setup) i also have two raid 0 arrays. So 9tb for each Array. I dont use any extra software like Softraid, but if i had that software i would actually run it in a raid 5 setup instead, but im not paying $180 for that when I just BD-R DL burn/backup all my important stuff to my other 3tb wd red drive (external usb 3.0) which is also setup as a time machine drive for all my Mac's (5 partition's. one for each mac and one for my backup files all connected through the server using the mac osx server software).
I'm also running an sm951 256gb as my main drive which is an overkill for my server, but it'll be nice to have when i decide to start using the server as a computer later (probably if i decide to sell my 27imac) I have a second mac pro that's running two x5670's and that's my wifes computer. I choose the sm951 mostly to free up a sata 2 slot by allowing me up all 6 slots for my WD Red Drives. I also have a usb 3.0 card in my computer and the stock raiden gpu that came with the mac pro.
Since your usb 3.0 card also has Sata you can run all 6 hard drives and keep your dvd-rom or Bd-rom (if you upgraded) by using
this cable. Then you run the extra power that you get from that cable to your bd-rom drive (or dvd-rom) and run a sata cord to your usb sata card.
Encase your wondering how i did this; You actually can fit two WD reds and a BD-Rom in your drive area. What you have to do is move the BD-Rom (or dvd) down 1 slot, then throw the two WD reds on top of it and it slides back in and fits. If you leave the dvd-rom on the top it wont slide back in with two 3.5in hard drives. The two drives fit when ontop of the drive because because of the aluminum bracket opening at the very top. It took me a little while to figure it out, but once i got it all together it works great.
Cant help you on the gpu question, since i dont plan to upgrade. I hope my experience helps you.