Just to offer a differing opinion...
My dislike for iTunes is so deep and immense that turning Calibre into an iTunes lookalike fills me with dread. Vital functions becoming teeny buttons at the bottom of the view. No sign of the search bar (which is the "most practical" way to use calibre for many users, particularly with large libraries) and restrictions. There are reasons why the toolbar has buttons with dropdown menus - there is a lot of functionality which people use that cannot be replaced with a buried icon somewhere.
You will also need to keep in mind that one of the biggest challenges I find is squeezing space for columns into the main view. So that will put constraints on for instance the tag viewer on the left as to how "wide" it should be as a workable default.
Sorry to sound negative. I don't think anyone would claim Calibre is "pretty" in its current design, but it is "practical" for users who have got past the initial learning curve. I think using a cross platform UI toolset to try to design something that looks decent on all platforms is a tremendous challenge that is not to be underestimated. Only recently I asked chaley to move a couple of buttons on the edit metadata dialog and from what I hear there was many hours of pain involved.
I applaud the intent and your incredible amount of effort in the mockups. I just merely offer a varying opinion to the thread for balance
