How to use the _S framework

The readme in the theme repository answers your questions already: replace what you don’t need, and add your own code to the theme’s style.css and functions.php.

The theme isn’t meant to be complete, it is really just a start. You can do whatever you want, and it will be fine.

Examples

I would change the font size handling. In _s it is set in px. This isn’t really user-friendly, because it might break when a user has set a minimum font size. You can replace it with better values sized in em.

There is a function _s_wp_title() to change the output of wp_titel(). This is plugin territory, so you can just remove it.