What is the best tweak?

Each system is different, for example my CDP isolation device works great on my Sony but does nothing for my friends tubed Metronome CDP. My friedns Elrods made a huge improvement in his system but only a nice change in sound in mine. My biggest improvement was speaker spikes with the B&Ws but no so much with the Talons.

The basic answer is that you have to hear them in your system to see what works for you.

Happy Listening.

Room acoustic by far. The biggest difference in sound will come from this area whether good or bad. If you have "good" sounding equipment, tweaking is just what the word means. You are squeezing the best performance of what you already have. Whether that performance is good or bad is up to your ears to decide.

Since your hearing is the most important aspect of hearing sound, I'd suggest the best tweak is having your ears cleaned of any wax!

Careful speaker/listener positioning and similar setup issues are critical. They also cost next to nothing.

Ear wax removal. Seriously.
Better and cheaper than most anything else.