I think the major win point with the Mini-ITX systems is that they are designed, and indeed, can be run, totally passively cooled. I.e. silent. It's easy to get pretty silent drives now (even 2.5" drives - you can get drives designed to run 24/7 now - HP's servers come with them now) so you can have something pretty powerful, small, and quiet.
You can make a PC mostly passively cooled - my media centre has a huge chunk of copper in it with no fans, and just a single case fan. That runs perfectly fine. I even fashioned a cowling of a sort out of some plastic to drag air right through the CPU heatsink so it was then dumped right out the side. That method can get costly as these big passive heatsinks can be very pricey. Underclocking the CPU helps.
I'd recommend
QuietPC for such things. Incidentally,
Noctua fans are THE quietest fans I've ever used, and come with a world of fittings and speed adaptors. I've got a 12Cm fan in my PC which is effectively silent!