Long speaker runs are to be avoided when possible. Since the length of the cable affects resistance, you can offset the longer runs by using a larger diameter cable.
Interconnects can be more prone to picking up EMI/RFI, but other than that, the losses are far smaller with line levels than with the output stage. If you have long interconnect runs, try to use balanced interconnects to cut down on noise. I would much rather have long interconnects and the amps close to the speakers if there is an option.
I've got my stuff behind the projector screen in a storage room. I've found whether watching movies or listening to music, it's a lot less distracting not having a room full of blinky lights.
The only thing in the listening room is a universal player. For music, the projector screen retracts and there's a door behind it that allows access to the rest of the gear in case I want to play vinyl or make some adjustments. An RF remote extender allows control of the devices that are out of sight.
