I've been running QubesOS as my main desktop since 2015. It provides good security, by running applications in different Xen VMs. However, it is also quite slow and has some hardware problems. I've recently been trying out NixOS, KVM, Wayland and SpectrumOS, and attempting to create something similar with more modern/compatible/faster technology.
This post gives my initial impressions of these tools and describes my current setup.