Personal opinion on things to stay away from:
- Akismet, it has terrible surges of false positives and operates as black box;
- external comment systems, they are solution in search of a problem.
I started with native WP tools alone. Blacklist is great, but takes some maintenance.
Since spam grows with time later I ended up building my own anti-spam plugin (combination of learning blacklist and simple pattern recognition). As of now I get over 10k spam comments a month and have to deal with 15-25 a day manually ( ~95% effectiveness).
Basic trade-off is the more you let computer decide the higher possibility of legit comment getting nuked.
So you need to find your own set of tools that provides:
- amount of control that you are comfortable with
- for the amount of spam you get
- and how willing you are to risk occasional false positive