Currently my main culprit of poor performance is MySQL and I'm not DB savvy. So far, I've had little luck in optimizing MySQL configs on my server, which has a Sandy Bridge processor with 16GB RAM and SSD disks serving a Drupal 6 site running on top of Ubuntu. I have ~1300qps with 80/20 read/write ratio. MyISAM is the only engine that I use (My experience with InnoDB have been horrible, despite all buzz about it as being superior to MyISAM).
The original my.cnf shipped with MySQL 5.1 is abysmal and Debian's suggested configs for 'huge' servers seemed to be less than optimal for my case. After a lot of experimentations and tweaks I figured out that tuning-primer script is too generic to give sensible advice (if they are not outright misleading!). So regarding the plethora of parameters involved in an optimal MySQL config, it would be great if some DB-informed drupalers could share their my.cnf for similar Server/case.
Best Answer
If you're running at that load on that hardware, you really should get some experts in to do this for you. Pythian and Percona are 2 consultancy/support organisations that I can think of: I have no link to either of them BTW.
Each install and load has different tweaks needed. The "huge" cases for my.cnf files I've seen are what you'd use a few years ago or on your mobile phone nowadays...
The default settings are amazingly low so if you've never changed them then there is your problem.
Edit: Have you already hacked your my.cnf? https://drupal.stackexchange.com/questions/12085/default-to-myisam-instead-of-innodb-in-drupal-7