Executive Summary: it's Studio/32* and/or Deluxe Paint Reloaded.
Here's the deal. When you want to produce absolutely precise bitmap graphics, e.g. for use in a 2d game or as part of a user interface, having a tool that doesn't precisely hit pixels and pixel boundaries is amazingly frustrating.
In Photoshop you've basically got the pencil tool and the marquee tool, everything else is useless. Pixel Ninja aims to fill this need, and it will be supported precisely because I often need it in my day-to-day work.
Pixel Ninja will be released as shareware for $20 when it's ready. Until then, it's free for personal use, and anyone who provides useful and constructive feedback will be entitled to a free license when Pixel Ninja 1.0 ships. I reserve the right to define "useful and constructive"!
The current version of Pixel Ninja expires at the end of September, 2009.
I will shamelessly rip off the best features of every graphics program I've ever used in an attempt to produce the perfect pixel painting tool. (There will be some compromises, e.g. I love Studio/32's "tab to toggle the eyedropper" shortcut, but I also love Photoshop's "tab to toggle the UI" shortcut. What to do?)
I don't really care about speed. These kinds of graphics tend to be small. Studio/32 was a pedal-to-the-metal program in its day because it was pushing the envelope. I'm not and I don't care.
I do care about leveraging modern hardware capabilities such as fabulous alpha channel support and filters. There are plenty of great programs for applying filters, so this isn't a priority, but translucent drawing tools are hugely better today than back in 1991 when Studio/32 was around.
It's the usability, stupid. I want this to be a fantastic tool for novices and experts. This means intuitive tools and powerful shortcuts. Who knows, maybe even scriptability and plugins. We'll see.
It's early days yet. So early, Pixel Ninja doesn't have a version number. (Edit: now it does!) I hope to have it polished enough to call it version 1.0 some time next year.
Note: * There was also the 8-bit Studio/8, which had its own virtues. But even if you're working with palette-based graphics, a 32-bit paint program along with (say) GraphicConverter to manage the palette reduction works fine.
It's been a long time since anyone produced a good pixel-centric paint program for the Mac. The last even vaguely decent one was probably Brushstrokes (published by Claris, briefly) which was itself an unashamed clone of Studio/32 (produced by Electronic Arts). Studio/32 was really Deluxe Paint (same developers even) but with 32-bit graphics, alpha channel support (back before Apple had put it into the OS), layers (well, a layer), and the slickest keyboard shortcuts ever.
I was told by an acquaintance at EA that Studio/32 was used internally by game artists for something like a decade after it stopped being shipped and was still considered indispensable. I can believe it.