Spider-Man The Sinister Six
Spanish Release - DOS (1996)
This one is very simple, since the game doesn't use MSCDEX, we discard looking for a device check. Instead, the game is checking for the files being located at a specific path, C:\SPIDER\. The drive letter gets overwritten with the value in SETUP.CFG, but if we leave that empty, it defaults to C:\ again. But to be able to run the game from any path, we simply empty the strings \spider\ and %c: on the executable.
However, there's another problem. For some reason, the game deletes some of its own files, required to play the game. Whether this is intentional, as a security measure, or it's just a weird unexpected behaviour remains a mystery. To overcome this problem, setting the game folders and files as read-only prevents the issue.