The attack surface of Xen, the current hypervisor of Qubes, is smaller compared to browsers and OSes that have 0days pathed several times a year. Even most Xen vulns don't affect Qubes.
I just can't imagine putting my whole digital life in one "normal" OS and hoping that the OS or browser security will keep me safe. I'm mentioning the browser because a lot what used to be in the OS is now in the browser, so it's functionally like another OS.
From a usability point of view it's also useful as I can have different environments. Not only different tools in each VM which means I can pretty much forget about dependency issues, but also different data in each VM. If I wanted, I could run any agent or malware on a VM and the exposure would only be whatever data I chose to put in that VM.
Of course, if you're not passing data between certain VMs, you could use different computers for an even better security.