I'm hopelessly inexperienced, but I want to do this as well. Getting USB (even for just keyboard and mouse emulation) and networking, in addition to high resolution video seems like it could be possible using one of the more powerful SoC's.
Really the big interfacing issue with a classic Mac is video, because many modern displays can no longer handle their sync frequencies. Either you need an older CRT (and to maintain it) or an older CFL-backed LCD (and to maintain it) that can hopefully show an image at a non-native size without upscaling.
With a custom digital video card and DVI/HDMI output you can actually hook up a modern display, just as with the card the OP created for Amiga. But unlike with Amiga, the classic Mac always used a straightforward framebuffer, so there's no software support issue.
All you really need are the level shifting buffers just as with the Zorro interface, and enough I/O for the 50-some NuBus signals. That breaks down to 32 address/data lines, a few NuBus control lines, and some lines to control the level shifting buffers.
Because optical ADB mice are hard to come by? There are a few, but they're rare.
A good USB implementation might also allow you to hook up storage devices, which would be pretty nice.
There are other (non-DIY) USB-to-ADB projects out there taking shape, too.
But I'm also hoping someone starts making Nubus cards for VGA, USB mass storage, etc. It would just take an FPGA or perhaps even an overclocked teensy.