mounting /nix/store from the host into the guest works with as many guests as you like - this is what the nixos tests framework does all the time, you just need a different "system" derivation for each (different) VM.

The problem with that is that the VM can see all the needless software, so if your goal is isolation, having a smaller closure is much better from a security point of view: if there's no coreutils bash etc then there's no risk of getting a shell spawned by an attack...