Here's my opinion, for what it's worth.
Making new 486 motherboards is a really cool idea, but there is little practical or economical reason to do so. Maybe someday when working original 486 boards are rare and very expensive. That said, I love the idea, and I would definitely enjoy building one as a kit.
I believe that video performance will be a major sticking point for most people. Implementing the VLB or PCI bus does not seem trivial compared to slapping everything onto an ISA bus. If you provide no VLB or PCI slots, then your video FPGA reproductions would have to be either perfect or have the ability to flash bug fixes.
I think modernizing I/O is actually a tricky subject. What should the shelf life be on one of these motherboards? Compact Flash is a good illustration. CF cards are basically obsolete these days and will eventually go away completely. A motherboard modernized with an obsolete CF slot is pretty ironic, and will be pretty annoying when CF cards become impractical. You could opt for SD cards instead, but you'll eventually run into the same problem. In my opinion, the best way to keep an old motherboard from becoming obsolete, is to make sure it has period correct I/O and put all the modern connections on the adapters.
This gives me an idea: rather than embedding non-486 era I/O onto the motherboard, create an EISA or PCI super I/O card with contemporary connections (USB KB & Mouse, USB/SATA/SD to IDE, etc.). This I/O card could be replaced with a newer one if the interfaces become obsolete.
You may want to research industrial computers. The 486 platform is very common in older industrial applications, and because those machines have service lives in the decades, newer 486 chipsets and boards are actually fairly common. I think the major problem with many of these newer 486 implementations is form factor. Many don't fit in a standard case or they have a PC104 header instead of ISA slots, etc. Others have some compromises in the integrated graphics or chipsets making them unwieldy for playing games, and some of them don't implement DMA on the ISA bus... My point is that the technology is there, it's just being made for industrial applications rather than for PC gaming. You may not need to mess with FPGAs: many of the chips that went into these industrial computers are recently-obsolete rather than obsolete-since-the-90's. For example, you could get a supply of the ZFx86 chips that Jakethompson mentioned,and build a modern form factor motherboard with a PCI slot and a couple ISA slots. This strays from the original idea of using existing discrete CPUs, but something like the ZFx86 chip (System-on-a-Chip) would eliminate the need to design your own chipset from scratch.
Coincidentally, I found this product (probably unobtanium), that's almost exactly what I just described: https://www.esapcsolutions.com/product/esa-in … hared-pci-slot/