"The Last Lecture", by Randy Pausch. While it's by a well-known CS professor (who was dying of cancer at the time), it's not a technical talk, but about life and work, and how to make the most of it. One of the most inspiring things I've ever seen.
https://www.youtube.com/watch?v=ji5_MqicxSo
Another fantastic one is Steve Jobs' 2005 commencement address at Stanford: