I'm actually near the end of my own HVAC-leak-chasing escapade. The original builder of our home had an HVAC installer who was either rushed, lazy, incompetent, cheap, or apathetic, because the duct sealing is haphazard at best. I've been gradually relocating and resealing lots of our ducts, and there are some massive, gaping holes in a lot of the joints. The issue isn't so much heat loss/gain; rather, it's the fact that some rooms don't get nearly enough air, at least partially because of the shoddy sealing of our ducts. So our master bedroom feels great, but the other three bedrooms are hot in the summer and cold in the winter.
A bucket of mastic goes a long way, and it's actually kind of fun to apply. It's like thick, goopy paint, and you don't need to be particularly careful with it.
Another benefit of the process has been that I've found blockages and damaged/collapsed ducts that I've been able to fix as well.