I will probably get a lot of hate from this but Ubuntu is simply more mature than mint. I’ve used mint and it works. The main gripe with Ubuntu is its use of snaps for many applications. They are not ideal but they do work. The main problems you may run into with snaps is the same problems you will run into with flatpak, appimage or docker.
Its a little more complicated to get persistence but my current main boot flash drive I carry with me daily is a 128gb thumb drive running ventoy. Ventoy is great because all you need to add a iso to the thumb drive is simply copy the iso over to it. Getting persistence is a little more complicated but the ventoy installer has a web gui that makes it easier. The ventoy installer is available for windows and linux. www.ventoy.net/en/download.html
On my bootable flash drive I have Debian, Ubuntu, Mint , kali, tails and even a arch installation with persistence. I also have several other utility iso’s including hirens_PE. I have installers for windows as well. I mainly use the linux installations for rescue and diagnostics on windows PC’s. I have however ran machines with no hard drive at all for weeks at a time without any problems at all.
So using rufus to make a bootable thumb drive is okay for a single OS with persistence but you can use ventoy and test several distros to find what you prefer.