I'm late to this party, but I'll add my voice to those who advocate mastic. It's surprisingly easy to apply, and very effective. Earlier this year, I sealed many of the ducts in our basement, and DW says that it has made a difference in the comfort level in the upstairs bedrooms. It's not necessarily an energy conservation issue, it's a matter of getting air to the specific locations that need it (and sucking it back from those locations).
I'm no longer a fan of the aluminum-backed tape--many of the joints were (often half-heartedly) sealed with that tape, and it was falling off in many places. It's possible that the installer was using subpar materials, and he/she was certainly doing the bare minimum to pass inspection (i.e. no tape on the back side of the duct where the inspector wouldn't see it, and it's harder to apply).