I have used Little Snitch for quite a while, then switched to Hands Off because I liked its interface a bit better and the ability to set a rule that would clear at reboot was a win. I regularly block outgoing connections; tracking attempts by Google, Apple & Microsoft (no PowerPoint, you don't need to check in to Skype at each launch...), limiting a lot of apps to loopback connections rather than full outgoing connectivity, etc.

Another benefit is that once I get over the initial rule configuration hump (and it is a real PITA for the first week or two) what I end up seeing are the anomalies and so I can pay closer attention to what has changed or where something is trying to connect that I might want to think about.