What makes the biggest difference in sound quality?

Room.

Interestingly, the source seems to be be most important part.  Folks focus on the tweaks, but the turntable, CD player, etc seem to make the most difference.  There wasn't much talk about the source in the comments.

The room makes a huge difference with a lot of high end equipment, so I am not surprised that that came up a lot.  Some equipment, such as McIntosh, is designed to be more flexible with unideal room setups.  If you have an unideal setup, make sure you audition your equipment in your room before you decide.  That was probably the most expensive mistake I've ever made.

Next would be the speakers and how they match up with your amp.

Then the preamp.

Then the interconnects and speaker wires.  One thing I found was cost is not equal to sound quality.  For example, I use a very expensive interconnect between my CD and preamp, but the same cables sounded horrible between my amps and preamps.  A much cheaper set of interconnects worked much better there.  I still really don't understand what works best, but I've found through trial and error there can be large improvements between different interconnects.  Anticables have worked well in most situations, esp speaker wires.

Other tweaks can make a difference once you figured out the above.

A power regenerator is great with a turntable.

If you do vinyl, a good record cleaner is worth its weight in gold.

@ted_denney Ted, since you framed the question to cover all the products Synergistic Research sells, I can tell you that the Shunyata cables and power distribution devices I recently purchased made a significant SQ improvement over your cables and PowerCell device, especially for my dCS Rossini DAC/Streamer. 

It is very disappointing how many people didn’t read OP’s question and answer in a constructive fashion which of those 4 items made the biggest difference for amps and preamps. 

I think it may be a potential adverse reaction to self promotion.