Learn English – Is this compound sentence grammatically correct

TheFreeDictionary.com gives this usage note:

Usage Note: The suffix -wise has a long history of use to mean "in the manner or direction of," as in clockwise, otherwise, and slantwise. Since the 1930s, however, the suffix has been widely used in the vaguer sense of "with respect to," as in This has not been a good year saleswise. Taxwise, it is an unattractive arrangement. Since their introduction, these usages have been associated with informal prose, and they are still considered by many to be awkward. For this reason, they might best be avoided, especially in formal writing. The most obvious alternative is to use paraphrases, as in This has not been a good year with respect to sales. As far as taxes are concerned, it is an unattractive arrangement.

The meat of this suggests that using -wise to mean with respect to is considered informal and even awkward. I suspect that pushing the boundaries as you do in the examples to include such constructions as user interface-wise makes an awkward usage even more awkward, as your own instincts seem to suggest. I generally have no problem with informal speech or writing in informal settings or for emphasis, but whenever I feel I am pushing the envelope I'll pause, think, and probably recast the sentence.

"What is wrong with XYZ?" is valid regardless of whether XYZ is one thing or many, and whether the questioner expects an answer detailing one fault or many.

If the questioner wanted to explicitly indicate that he expects an answer listing multiple faults, he'd have to say something like "What things are wrong with XYZ?".

"What are wrong with XYZ?" is never grammatically valid. Nor is it a common mistake — I don't recall seeing it before now, and Google Books records only 14 instances of "what are wrong with", compared to millions of "what is wrong with".

As regards exactly why the non-standard usage is unacceptable, rather than just uncommon, what in this construction is a non-count pronoun. Non-count nouns require the singular verb form.

Edit: Kudos to JLG for highlighting the importance of the word wrong in this construction. The interrogative pronoun what attaches to wrong — a non-count abstract noun which transfers its non-count status to what. That doesn't happen with, for example, "What are those things?".