I agree with all those who say Gears 2 (especially after the first game!!!) and Fable II
My winner, however, is the final bosses of FF X. Admittedly, I had over levelled my characters massively, so it only too 2 hits from Tidus to take him down
Uncharted 1's had a reasonably tricky build up and FF XII's did take a while even if it was quite easy