Not any issues with resources, yet at least. Mostly related to user management (roles, giving access to specific sites) at the moment with the Team Control extension. As you can imagine we have quite a few people working on the sites and most of them need access to specific sites.
For example by default when creating a user role, all sites are selected and there’s no deselect all function, so at the moment it’d require 312 clicks to give a specific user access to a specific site. 
According to the MainWP devs this is in the pipeline and coming soon.
And need to create a role unique to each user if every user needs unique privileges, you can’t just create a MainWP user and give that user access to specific sites - permissions are tied to a role, not a user. Very minor issue though and just a slight extra step when setting up new users.
The Wordfence extension turned out to have a number of issues: Bugs in Wordfence extension plus what’s missing from that thread is that you cannot browse sites per site group, which would be necessary if you want to check/scan the sites from a specific server for example.
And by default the Team Control extension allows any user to access the regular admin backend and can from there escalate their privileges as they please - have devised a crude solution for this by redirecting ^/wp-admin/index.php$ to /wp-admin/admin.php?page=mainwp_tab which deters curious clickers of the “Go to WP Admin” button. 
Will definitely need to come up with something more secure/useful before scaling up.
Just some off the top of my head. There are tons of positives though - quite reliable client sync, the ability to add sites in bulk… in fact most of the issues are due to the extensions - the core product is quite excellent!