For Windows-based systems, I have seen that changes to the Registry or System Directories are some of the things which are used to track if a machine has been compromised. Similar things must exist for other platforms- and I must admit that I am unaware of them.
My curiosity here is that what are the best metrics which a security personnel may want to leverage (at the host itself or at the Network-admin level) to decide whether a system has been compromised, and do them in an OS-agnostic way? That is, these metrics should not change - irrespective of Windows, *nix, Mac, or handheld devices with Android etc.