What makes the biggest difference in sound quality?

You can make DIY Cords and fuses as good, if not better than most manufacturers. Pennies on the dollars, and it’s a lot of fun to experiment on your own. .

Copper foils for USB, and XLR. Solid for everything else.

Mineral oil+graphene+silicon dioxide for fuse dampeners.

DIY DIY DIY DIY. At least for the ones that are good with tools.

I bet there is an astounding percentage of hermit Agoners. Wow. To the OP, Speakers and source components first. But reality is, that is a MASSIVE variable with all number of possibilities. No easy answer. Power has to be second. If power sucks, so does everything else. Speaker cables next, then on down the line. And I too disagree that the entire loom much match, plenty of people making great music with a variety of cables.

You can make DIY Cords and fuses as good, if not better than most manufacturers. Pennies on the dollars,

If true then you are making cables for pennies that are better than the ones I bought for thousands. If true you would quit your job as they would sell like hotcakes. I would be first in line to replace mine with yours. In fact you would be nuts not to send me a set, just so I would tell everyone how great they are and you really could quit your day job.

Which is what Lubos did, so we aren't just spinning fantasy here, it actually happened. 

Now I can hardly wait for the DM, to find out which ones of your marvels you want to send first. The suspense is palpable.

The room

Speaker position

Rack position

Dedicated line

Cable management

Everything else

Interconnects, speaker cables, power cords, or fuses?

I must not have good ears, because homemade interconnects seem to as good or better than most of the store bought ones I have tried.

Keeping speaker cables short helps, and also keep em fat in diameter and bi wire them if possible.

I have not ventured into powercords and fuses.