Here's my suggestions. (Or should I say, -wishlist- for the most efficient Pixel Art program I could ever imagine?)
Now, instead of birthing a bunch of fat paragraphs that would most likely achieve nothing, I decided to go with the classic Pixelation way, edits and mock-ups. There's no better way to get messages across.

I'll begin with what I found. Overall, this version was fully un-usable for me, testing on a Cintiq. The screen was too cluttered, it was sluggish to change between tools (Time was wasted in long trips and menu back and forths), and as such, a frustrating program for any efficient drawing of any kind.
So here's my suggestions to fix pretty much everything:

I'll tackle this image by parts.
First things first-
Normal click inputs a drawing stroke, which is applied when the click is released, like in every other drawing program. That whole confirm render stroke issue needs to go, as it only wastes time. Usually,
Undo is what you use to revert pretty much everything.
Space key opens up a
customizable pop-up menu.
Right Click activates the
Colour Picker. (These two functions take the two buttons on my Cintiq pen, and are the most useful and essential.)
Just like in Graphics Gale. This pop-up menu is incredibly efficient and allows for tool changing in less than a second, for the experienced artist. The key here is customizable, it really allows this to adapt to pretty much anyone. I think a basic rounded list should be introduced as a place holder when opening the program for the first time.
Colour picker. Probably one of the most used functions in pixel art, and deserving the greatest shortcut. Right click seems a natural option, like it's done in Graphics Gale. One just can't live without this.
Top Menu. Tabs for open files. It's incredibly convenient. Eliminate everything else from here, as it makes the layout too charged, and there can be better places for both the zooming options (Tool options) and grid ('Image' top menu).
Tools window. Along with Painting, Palette, and Preview, these windows need the option to be free to drag around anywhere. Dockable as well of course. Otherwise, the whole interface feels too rigid. We artists need freedom here!
I put a number of tools there that are used frequently. Select tool, lasso select, magnifier, they all go here.
Painting window. It's reduced to basic
pixel brushes, their
size, as well as pixel textures (A feature in Graphics Gale). The latter can be optional, but it's very useful sometimes. Those are the essentials. Anything else, like the solidity levels as well as any other features one might want to add, should be able to be hidden away in a tab, to
free space off the interface and add it to the actual drawing.
Palette window. Added
primary and secondary colour options. Also, the ever-useful
RGB slider, with buttons to click right away with your drawing pen, as to avoid touching the keyboard. Everything else seen here is more of an optional thing, and should be able to be hidden away under tabs if so the user prefers.
Preview window. It's simply too vital in pixel art. Should have many zooming options, with at least 50%, 100%, 200%, 300%, 400%.
And that's about it. Here's a sample configuration I would use, to serve as an example:
Everything I need would be there, and the tools in the tools window I would place in the
Spacebar menu, for speed and convenience.
Less is more. But in drawing, less interface means more un-obstructed drawing.
