The WordPress Multi-Site feature has some great advantages if you manage multiple blogs. From a single login and control panel you can manage them all. You have just a single WordPress code base to worry about. (Think about that the next time there is a new WordPress version and you have a dozen blogs!)
We manage a few WordPRess Multi-Site installations and what follows is based upon our first-hand experience:
The core Wordpress files are pretty stable We've not had a problem initially enabling Multi-SIte nor have we experienced any problems with version upgrades (We recently did a version up grade for a Multi-Site user from WP version 3.0.4 to 3.6.1 and it went very smoothly.) The caveat however is that we've developed our own written procedure for enabling the Multi-iIte feature.
The problem is plugins. Most plugins are not written to accommodate Multi-Site mode. Let's say that you have the 'main site' at foo.com and are Using Multi-SIte to create and manage blogs at:
While the plugin code resides at "foo.com/wp-content/plugins", unless the plugin supports Multi-Site it will think it is at "foo.com/Blog1 (or Blog2 or Blog3)/wp-content/plugins". The result is that the plugin cannot find it's own internal files it is looking for.
The take-away is that before you consider Multi-Site you should verify all your plugins support it. Sometimes the only way to do that is to erect the whole thing in a non-production environment and test it yourself. We've often found ourselves digging into someone else's plugin and modifying it to support Multi-Site because our client needs the plugin and the plugin's author is unresponsive or cannot be found.