Mellissan from Baldur's Gate 2, Throne of Bhaal Expansion. To all you liars out there who said it was easy... BAH!!!!
Mind you, she IS defeatable, but even doing it is tough stuff.
Complete Magic Immunity, She casts Time Stop, removes all protective magic from your guys, curses them with a -10 malison (If you know your D&D rules well it's a REAL downer) she casts Balor demons and God knows what, has 4 phases, and her melee attack paralyses you. She's also immune to all but +4 weapons and above (To put it in perspective, there are about 5 decent weapons in the entire game +4 and above)... and it takes searching.
Mind you the Battle music Rocks so hard you won't notice you're dying miserably