Keep the ability to draw using a brush. Of course this brush would be 32-bit with alpha in new software.
I like your tool ribbon at the bottom, that could go a long way.
Proper zoom is essential, as well as keyboard shortcuts to select colour. In paletted modes in DPaint [ and ] did this, in 32-bit modes you might need to have R,G,B and A adjusters.
Keyboard shortcuts however is what is most important. Especially for fine pixel work, one hand on mouse, one hand on keyboard.
Look at the Gimp and see everything it does wrong for pixel work. Windowed interface that gets in the way, awkward to scroll around using keyboard when zoomed, poor shortcuts, and so on. Brushes are only from the preselected options (including a bell pepper, what?!). It's like a cross between Nintendo SNES Paint and Photoshop.
But first, work on that graphical tool ribbon idea, see if you can get that working efficiently. Keyboard shortcuts that work depending on your selected tool pane can alleviate the issue of having too many functions for the available keys.
And note how poor colour pickers are in Gimp and other tools. DPaint got it right, by necessity and system limitations of course, you need to be able to select certain colours instantly, without opening a "colour palette" window and clicking around for ages. And this colour area needs to be large enough to be useful - no 32x32 picker area. I can see a system where your tool ribbon can be accessed with shortcut keys 1 .. 0 for example, so you can switch to the colour ribbon and use the mouse to select a colour, smoothly and quickly. You know where the colours will be. No pop up window. No clicking to change the colour from that. No "add to custom colours" that overwrites the previous colour you saved.
