Hey there,
I’m sure you know http://versionpress.net already. They just turned fully OpenSource last week.
Their setup guide is checking if everything is great after the first installation and it is trying to secure the directory where the DB is in. Of course .htaccess doesn’t work and automatically configuring nginx config isn’t possible otherwise. Also they do their best to support non-standard directory/file layouts of WordPress.
I’m not sure how but maybe it could be a good idea to somehow build in support for them so the relevant directories are secure. I guess quite a lot of power users and WP devs will use Versionpress at least when it is finally out.