I've built software with a configuration database (Windows registry) and with flat configuration file-folders (*nix). I feel like I'm running in a circle because the trade-offs are so equally balanced that there's no best-case. From considering backups and database consistency, to tripwire malware detection of changed settings, to automation of access, to consistency in naming, retrieval, and type conventions, to self-documentation, to backwards compatibility... At this point I'm not even sure I would understand the correct or "best" methodology if it was handed to me on a silver platter.
So a database then?
If by database you mean "relational database" – I'm not sure the relational model is the best fit for a config store. I think a more hierarchical database model is more natural for that purpose. (Of course, you could use a relational database as an underlying implementation detail – LDAP is fundamentally a hierarchical database, but there exist LDAP servers which store the data in an RDBMS, for example Oracle Internet Directory.)
The Windows registry is a bad implementation of a good concept.
Imagine if the registry had a schema with embedded documentation, foreign key relationships, a packages database with each key owned by a package, etc...