If you have the memory, and you can live without GPU acceleration, there is really nothing like Qubes. The biggest benefits to me aren't even the security aspects. It's the ability to test things without worrying that anything unrelated gets affected.
If you want to install some random piece of software, especially commercial software that always comes with an install script (or worse, a binary) it's very comfortable to be able to give that program a dedicated playground. When I want to uninstall it, I run qvm-remove vmname and it's gone.