Just trying to stop a war before it starts...
So in practice, the 'MAC address uniqueness' is not strictly true, but is a very reasonable assumption. The 'uniqueness' must be guaranteed for you to have a functional network. So, at least on your local LAN, each MAC address—whether it be hardware-based, spoofed, or synthesized—must be unique.
'Clever' programs running on your machine can weed out all the synthesized and spoofed MAC addresses used by your box, and obtain the [size=-2](one or more)[/size] real, hardware-assigned MAC address. Keep in mind that if your machine is using a spoofed/synthesized MAC address, then you must have at least one hardware MAC address available. Most modern machines have at least two hardware MAC addresses—one for the wireless 802.11 adapter, and one for a wired 802.3 adapter. So, even if you've spoofed or synthesized a MAC address, it will be meaningless in the presence of a 'clever' program. And 'yes', there are techniques for obtaining this information that work even in the presence of VMs.
chinajade
Interesting comment, Chinajade
You are right in the fact that each Network adapter on your comp will have a different MaC. But, what prevents you from changing them all?? I mean, if you are going through changing/spoofing one of them...why aren't you changing the rest of them? It's not like it's hard. Or obvious.
So, the "more than one MaC Addresses" part is not that important to its uniqueness. Specially when there are plenty of HardwareId's and Guids that you can't spoof with that ease...or even at all.
About the techniques to obtain the original MaC Address info of the active network adapter, and ignore whatever spoofing has been done, I know nothing.