I would love to see a modern Operating System built off of SmallTalk. I tried out Pharo recently and I was amazed at its ability to introspect (reflect?) into any ui element in the running image and see/change the code for that element. I think building an entire Operating System on this concept would be really cool. The level of extensibility we would get combined with the ease of extending the OS would lead to some pretty awesome changes.
To get around some of the common pitfalls of new Oses it could use a rump kernel and leverage the drivers from Netbsd, and it could be developed on an SBC making it easily accessible to people to run on actual hardware
A recent start on this could be the NopSys/CogNos project, which built a standalone Smalltalk system on x86 a few years ago. There are GitHub repos[1,2,3] and a paper [4] where the authors write "there would certainly be much more work needed before one could consider deploying our system." The project seems to be inactive now.
1. https://github.com/nopsys/nopsys
2. https://github.com/nopsys/CogNOS