It would be pretty easy to, say, bring a patent suit against two random WINE developers and five people who admitted to running Steam games on Proton.
They might not win, but they don't necessarily have to win to scare a lot of people out of doing the thing they don't like.
Probably the more dangerous approach would be: now Windows 11 update XX flatly refuses to run un-notarized software, unless Windows Defender saw it before X date. To get your software notarized, it has to validate that it is running on genuine, non-rootkitted Microsoft Windows using a TPM attestation from the boot process, for Important Security Reasons. Microsoft has a patent on this mechanism that your software would necessarily infringe, but they're happy to license everyone to use that patent as long as the resulting software builds are in turn licensed to run only on Microsoft Windows, a license term with the mechanism helpfully enforces. Any software to bypass this and patch out the checks is clearly an illegal circumvention device for an effective digital rights management scheme, and therefore all gamers go to jail for 1000 years for contempt of business model.
Well you can start by trying on purpose to make an SCP wiki level horror scene. Then the bugs are features!