Rearrange the order of words:
The matter with you is what? Now the subject is obviously "matter".


But you are presuming, dr. bill, that such rearrangement of the sentence does not alter (but merely makes more evident) the subject of the sentence. I suggest that that premise is faulty, and that the rearrangment changes the gramatical subject where the verb "is" is followed by a noun. Contrast for example:

Property is theft. with Theft is property.