OK, I thought I would help users out who have this hiss problem.
I had the problem in my old system, but I had the luxury of building a new system a couple of days later.
Just to be clear the problem I had was interference from Hard drives, mouse movements, through both my speakers and my headphones with nothing else connected.
To my knowledge this is a ground issue, BUT NOT WITH THE RME CARD
When I took my old PC apart I noticed that only one of the fixing holes on the motherboard is marked as grounding point (I needed to do quite a bit of research to identify this) Also on my Case (I have used the same case for 3 systems) I noticed that only one of the motherboard fixing pillars was Metalic (Ie: For case grounding) in this case the metalic pillar did not correspond to the grounded fixing hole on my motherboard, hence THE MOTHERBOARD WAS NOT CASE GROUNDED
Now this was not an issue prior to getting the AIO because a was using an EXTERNAL MOTU interface.
It is unfortunate that the AIO is such a sensitive device that it exposes promblems with a computers grounding system. A good grounding schema on a computer should achive near silent operation of the AIO (as I have now)
Unfortunately, not every one has the luxury of making a new compute, but anyone who does build a system should be aware of motherboard grounding.
If you are experiencing the noise/interference problem, I advise that you get techy, read up on your motherboard and confirm that it is indeed correctly grounded to your PC's case.
I'm going to speculate here but I would say the grounding issue of modern computers is much more wide spread than we imagine, the harsh reality is that PC manufacturers arent aware of it because so few people actually use INTERNAL High quality PCIE sound cards, Casual users are satisfied with onboard sound (which is also suceptable to this problem on cheaper motherboards) and many pro users opt for external interfaces (That said, those of us who use the PCIe AIO know the benefits of ultra low latency when using PCIe) so this problem goes un noticed in the long run (it doesnt affect the performance of a PCIe video card)
I'm no grounding expert so there is probably more you may need to know/read to resolve every instance of this issue, but in the case of big name manufacturers such as Dell, HP & Apple I would suggest you make them aware of the issue, confident in the knowledge that this problem resides with THEIR grounding schema and not the PCIe card.