There's not really an exact science to it, but manually-optimised code is usually more structured/systematic to make it easier for the human author to manage the dependencies and state across the board, while automatically-optimised code is free to arrange things however it would like.

As an example of the kinds of optimisations that the best human programmers were doing before compilers took over, see Michael Abrash's Black Book: https://www.phatcode.net/res/224/files/html/index.html - you can intuit how a human might organise their code to make the most of these while still keeping it maintainable.