I'm surprised nobody has mentioned Qubes. You can run both Fedora and Debian on it, out of the box.

It's "reasonably secure", which is otherwise translated as "very very secure" compared to the typical approach where everything is installed and executed on a single machine using a single (sudo enabled) user.

YMMV but for me it's great to have work stuff in one qube (using work VPN), personal stuff in another (using personal VPN), a dedicated qube for my password manager, ability to quickly throw up disposible VMs for trying stuff out, etc etc

I never have to worry about 'some app I installed ages ago' and if I did, I'd just recreate that particular qube (no machine downtime)