My question holds for fully observed phenomena as well as theoretical ones.
Michio Kaku, when talking about the Kardashev scale, stated that a Type II civilization is virtually immortal and that no known force to science can completely wipe out a Type II. I'm not sure about that, at least considering future realizations.
1. What is the most powerful man-made force today? I'm pretty sure it's the nuclear bomb, but I could be wrong.
2. Natural force as today? I would think a supernova, a gamma ray burst, maybe even a super-massive black hole?
3. Time for speculation? What could, within reasonable bounds of speculation, an advanced future civilization create to yield maximum destruction?