Ad Optimization is a balancing act between Time, Money and User Experience. It’s very hard to have all three, even when it’s your job.
You can spend enormous amounts of time running and analyzing reports, trying to squeeze a few more pennies out of your setup, but it’s a losing battle subject to diminishing returns after you’ve got a solid stack. (However, do make sure you’ve got a solid stack!) This waste is insidious because it happens one hour at a time while you’re playing email tag with ad networks or trying out new codes on your site. As a sanity check, try to estimate from historical performance what would have happened if you’d done nothing instead. Just don’t waste too much time doing it!
You can also destroy your user experience while trying to make an extra buck. Adding too many units will slow down the site. Working with low quality networks that allow autoplay ads or heavy creatives can quickly damage your users’ goodwill. If you’re too careless, you could seriously damage your site’s reputation. However, it’s a tradeoff. Trying to maximize revenue while maintaining a good user experience takes time, following up with users, attempting to re-create issues, and corresponding with ad networks.
Take an 80-20 approach. What part of your advertising operation is most effective?