I have running some sites on Multisite and I think it depends how you want to manage them.
First and always is backup. There is not much great backup plugin for MU.
You will need one who can backup and restore the subsite when it get crash or something else.
Second is plugin menu. As we know that every site owner's needed is different, some will buy plugin for them self and some may not. So, you gonna need how to control what plugin hide or not.
Third, cache. We also know performance is also important for site grown. However when I active the plugin like W3-Toal Cache or others. Honestly it's very hard to tweak for each sites needed. So I give up to use them and just tweak for Nginx.
MU also has a congenital defects of server respond time. Maybe it's because the domain mapping. I used Google Pagespeed Insights to check every subsite and always get server respond delay between 0.2 to 0.5 secs. I have try to remove all the images on page and minify all the CSS & JS and HTML files but still get 0.2 secs respond delay and I think it's not about the server optimization tuning.
Last, is about the MU registration process, when someone register in a multisite, by default he is a user of all subsite. So he can't not register in other subsite because he already got one. How strange hum.