Personally, my goal is to have a cup of tea or a cigar in my left hand and my mouse in my right hand. So I don't use the modifier keys. My preset so far: just two columns for the wheel (seek, speed).
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I have no need for the volume adjustments, I use a few browsers, this way I get to adjust the volume in the default windows mixer (RB+LB toggles C:\Windows\System32\SndVol.exe. I had to use AHK to toggle the program.)
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For my old laptop I may add a third column to adjust the quality (Wheel or MB4/MB5). A quick jump to the next chapter might be handy. I don't know yet, the extension has so many things to bind, there are audio compressors, video filters, the dev is actively adding more stuff to his project. It really is a XMB for YT.
PS. Actually that guys has one more extension in development "Video Dominator" and unlike Tweaks it's a universal beast.
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