We have now more than 60 active website running on Craft CMS and have been able to keep our lives somewhat straightforward when it comes to the development side of things (eg. code repository access, deployment, etc).
The main challenge we are still faced with: how to central access or authentication (eg through groups in Google or AD) to the individual sites without having to create/delete users on each and every site when a new team member joins/leaves (too much effort) and without using a single login for all team members (too insecure)
Other challenges - how to have an overview of CraftCMS version installed on production - how to know centrally what plugins are used and what versions
I'm sure other agencies also have similar or other needs, what are yours?