Diablo 3 does not normally allow you to launch multiple instances on one PC.

You have the option of running multiple Virtual Machines on one PC, and each of them can run an instance of Diablo 3. And, obviously, this is going to perform poorly -- your GPU may not be fully utilized by Diablo in the VMs, and you're running extra instances of Windows what more needs to be said...

Inner Space and ISBoxer perform application-level virtualization, and in this way it is similar to having a virtual machine but without having to run extra copies of Windows. It runs natively instead, and will fully utilize your GPU, etc. This means it is much higher performance than running Diablo 3 in virtual machines, as anyone who has tried both methods will tell you. They will probably also tell you that ISBoxer is awesome and exhibit zombie-like behaviors.

On multiple computers, of course, multiboxing should work fine with ISBoxer and other network-enabled multiboxing software. HotkeyNet, etc.