The Archdemon from DA:O. Using the trebuchets would make too easy so I tried going at it with just sword and shield. That didnt end well...at all. :brokencomputer:
Would probably say virgil from devil may cry 3 2nd battle on Dante Must Die mode. This one was absolutely brutal for me with his phantom sword attack and required a bit of skill to master to defeat him. Other than him i've never really been challenged by a true game boss which kind of stinks.
Ming Xiao from Vampire: the Masquerade - Bloodlines. If you use guns and/or the Flamethrower, she's not so bad. But if all you got are melee weapons, ugh, good luck.