Minimal work involved. A bunch of emails back and forth, where we tell them our ad size if they provide an image. Or they provide a logo and we manually ad the text if they aren't technical enough to provide a custom image.
I'm very interested in learning more...
It definitely takes time and work to develop and maintain relationships, but we also get to keep 100% of the revenue. In some ways we've just decided that ownership of the relationship and process is more important than being able to quickly slap some Adsense code up on the site.
That said, we also used Adsense early on, but have been doing this for ~5 years.
People seem to have forgotten that users are most likely to be interested in what they are currently reading, because it is what their mind is currently focused on.
Because our content is so specific, ads which are relevant to the content end up targeting the user because you wouldn't be spending time on the site unless you care about the content.
We also sell the space per month as opposed to based on impressions or clicks so it makes it a little more straightforward.
We post about office design and our ads are primarily for office furniture or other services related to the industry. We also self-host the ads which are non-animated jpgs and sell them without using any ad networks.
What you describe works well for us :)