As a general rule, using one instance for multiple voices is more CPU- and memory-efficient. However, that benefit might be reduced or even become irrelevant if the instruments are very big, especially if you want to freeze them individually.
Looking at my current project I have up as I type this, there are three instances of Kontakt and two instances of Omnisphere. I could have done it all with one instance of each, but didn't, for convenience.
The Kontakt instances each have 3 (related) instruments loaded, the Omnispheres have one each.
For example, I have 3 percussion instruments in one Kontakt instance; because they're all related, I'll likely finish with all of them around the same time and can then freeze them as a group. The Omnisphere patches are short effects, not principal instruments, so I finished them quickly and froze them. Once rendered, it doesn't matter how many instances were used, because they're gone.