What is a way to keep the main system as safe as possible aside from getting a completely separate computer for just pirated software?
Would installing an OS on an external ssd and booting into that to run pirated software while blocking access to other drives in your system or physically unplugging them be one way?
Or are there better ways to isolate the software you run and use as much as possible?
I don't know where you guys get your stuff but if you have reasons to be this causious I would suggest having your important stuff somewhere else instead of the other way arround.
If you want to play games in VM you will probably need qemu/kvm and sepparate GPU for passthrough. Otherwise your VM will struggle to load anything serious. But I think others use that mostly to run windows apps on linux machine or simmilar.
Maybe you can just dualboot from 2nd drive, it should be 100% safe if you unplug your main drive, but thats probably overkill. Im no expert, just putting it here so you can google
I haven't seen your stance on VMs, but a lighter approach might be confining the software to an AppArmor profile or such. The kernel will enforce the restrictions on what it can and can't do.
It won't have the overhead of virtual machines, and you can keep using a single video card, but setting this up is quite tedious, though.