Of course Elizabeth also gets my vote, but I want to do something different, and mention a boss that isn't from an RPG, and isn't a final boss. Fans of the X series probably remember Crush Crawlfish from X3, and probably remember how much damage he does and how easy it was to get hit by him. Even with the special weapon he was weak to, the fight wasn't a sure thing like most of the others, at least in the first fight. Even with the weapon, unless you had at least half the heart tanks, you probably used a sub tank for the fight. Sure, the second fight was no problem when you cut him in two with the Z sabre, but that first time was really something.
-That optional boss with over 50 million hp in FF12 -Genshin from Ninja gaiden 2 (also in ninja gaiden 3 trial... I just never seem able catch on to his pattern, and needless to say he's such bad@$$) .. Actually lot of boss are tough in ninja gaiden series -final boss in Zero 3 -vega (claw) in street fighter 2 (CAN'T beat him with anyone except chunli haha)
...I'm sure there are more but those 4 are right off top of my mind at this moment