I am struggling a bit to describe the suggestion, so I will tell you what I am seeing and then my proposed solution to see if it can spark a discussion around what can be done (hopefully).
I regularly get 404 hits to files that obviously (to me and probably any real person) should be banned immediately (various attempts for php files in the root directory or other locations). I am not sure how Defender triggers a 404 hit, but couldn’t we have some optionally enhanced checking when its of a specific filetype (ie PHP/CNF/configurable) possibly in some configurable folders (or even the opposite where we exclude folders) such that Defender then does real (!file_exists(xyz.php)) checking and blocks according to the enhanced settings.
The standard WP 404’s tend to be cache files missing/pages moved etc and not so much PHP files that no longer exist.
Anyway I hope that helps start the discussion of the feature suggestion