I don't really have a question in mind, but I'm thinking of the kind of things that are covered in APUE(2e) which is POSIX, SUS, etc. C API mostly. Obviously generalized C programming is not ontopic, but what about the Unix C API? It's obviously Unix, but is it too programming for here?
Unix's shell interfaces tend to be pretty close to the syscall interfaces. In particular shell utility errors are often straight lifts of system call errors. So people who understand the one often can help with the other. Therefore I think questions about the system interfaces (i.e. the C API) should be on-topic here, as long as they're about common unix interfaces (not necessarily POSIX, but excluding very different systems like Cocoa) and essentially language-agnostic.
Note that this answer only applies to questions about issues like signal delivery, terminal modes, sockets, … which are exposed in similar ways in most languages. It can apply to other low-level APIs associated with unix, e.g. X library calls (that map closely to the X11 protocol) or D-Bus communication. If the question is about an API that only programmers would encounter (e.g. the C string library functions, the Gtk object model, the Linux kernel driver APIs, …), it's off-topic here and should be asked on Stack Overflow instead (or migrated there if it's already been asked here).
The guideline is: will the question interest only programmers, or also users and administrators? A sysadmin debugging why a server won't start with
strace output is on-topic here. A programmer debugging why his kernel module is causing an OOPS is off-topic.
Yes, the Unix APIs are definitely on-topic, as you need to understand the works to get anywhere: file descriptors, pipes, paths, permissions, sockets, processes... the list goes on and on.