Only thing I have enabled is Akismet. Think I've managed to dodge a lot of spam by not showing the comment forms to known bots; otherwise, I might have looked into additional things.
Probably best Anti-Spam thing I've come across in WordPress is [Anti-spam — WordPress Plugins](https://wordpress.org/plugins/anti-spam/) which catches 99% of the stuff before Akismet even sees it and there is nothing for a user to do.