Best Tweak???

New power cables, stands, contact enhancers bla bla bla... Lets be fair these all make hardly noticable or no noticable effects.
The biggest improvements You can get by tweaking are right SPEAKER PLACEMENT, ROOM TREATMENT and for mid-hifi and mid-highend speakers try damping speacker cabinets using special absorbing materials. This reduces boomy box sound and resonances, reduses brighntness and adds musicality. But don`t over try otherwise You loose in details and deepness of soundstage. For bright sounding systems is this the cheapest and more effective method to reduce harshness and add warmth.
These twaks all make easily noticable effects while higly expensive cables, stands and other audiophile stuff are hardly noticable.
This is only my opinion basing in my experiences and doesn`t claim for absolute verity.
Happy tweaking

Another vote for the Neuance shelves. They work wonders especially under power conditioners. Another tweak would be to separate all your cables and lift your speaker cables off the ground.

removing the split glass doors from the front of a wooden rack was among my most startling & unexpected system enhancements. Whether they were closed or open, those doors caused some significant degradations

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Symposium Rollerblocks....simply amazing. Go for the grade 3 tungsten cardbide balls option. Try one set under your CDP and then try your pre-amp, power conditioner and amp...It will be quite a surprise.
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Mapleshade SilClear is an amazing tweak! One small jar will last a lifetime and the difference in clarity, detail, and overall smoothness is nothing short of spectacular, and I was using Caig Pro Gold before but this stuff takes it to another level!

Another great tweak is to use Exact Copy to record CD-Rs with your computer system. The new copies sound much better as noted above and Exact Copy does a much better job than Roxio or the other duplicators.

However room treatments and setup detail make even a bigger gains in a high rez system. Try some Vibrapods and Vibracones. This is one great combo that doesn't cost a bunch either.