Ok ive noticed the interference stops when i unplug the USB from one of the externals, even though the drive is still on (running from external power source).
Anyone have any ideas at all?
Don't quote me on the specifics but I thought I remember reading that there was a problem reported a while back about RF noise leaking from USB 3.0 cables and/or devices when they were plugged into the some late-2012 Mini's USB 3.0 ports. I believe it effected 2.4Ghz and Bluetooth devices including the Mac some Mac Mini's internal Bluetooth Tx/Rx radios. It primarily effected the useable distance for the Apple wireless keyboard and mouse/trackpad. There was a shielding repair kit available to fix the Bluetooth issue for Mini users who experienced this problem. (Since then I believe Apple has have improved the shielding for the Mini's Bluetooth radio.)
For interference problems with all other devices there was a solution to use better quality shielded USB 3.0 cable and better shielded USB 3.0 devices (external HDs, etc.) If this interference problem is what is effecting your sound you could use the above solution for cables as well as using higher quality shielded audio cables and better shielded speakers.
This noise issue from RF interference is not an uncommon problem. I know from experience that some cell phones can transmit interference to computer speakers. A few years ago I used to hear clicking and static immediately before my cell phone rang or before it received text messages. This happened whenever the phone was near my computer speakers. When I changed to a different phone the problem went away.