If a GitHub user fails to respond to a DMCA request, and GitHub doesn't remove the content in question, GitHub as a service provider would then become party to the complaint under the copyright safe-harbor rules (a suit that GitHub would definitely lose, and can have fairly drastic downstream consequences for their status as a safe-harbor going forward).

It's not that users are irrationally responding to DMCA requests when they don't need to, its that as a service provider, GitHub defaults to a stance where a claimant's DMCA is automatically processed if a repo author doesn't reply within 1 working day. This effectively means that for DMCA requests of all types on GitHub, "no response" is synonymous with "I'm guilty of infringement, plaese take down the content".

A DMCA claim response in GitHub is admissible as testimony should the case ever make it to court, and therefore carries the penalty of perjury (both parties are informed of this before opening/responding to the claim in the GitHub UI). So unless the repo author is absolutely certain that they're not hosting DRM circumvention software, they have little-to-no recourse but to allow the takedown request to go ahead.