Hmmm...This'll take some thinking....
Actraiser had some pretty wicked bosses...
Then again...there is that 2 screen tall Triceratops Guy you fight in the Reverse mines in SotN.....
Ridley was Really hard in Super Metroid,
That brings up Omega Pirate in Metroid Prime( I was fighting him for 3 hours over Many, Many Attempts my 1st time)...
And then in ZoE2 when you fight Jehuty inside the Compressed Space....God....Took Me Months! (literally!)
But Truly...Nothing Can compare to the Final form of the Last boss in Panzer Dragoon Orta. I mean, Practically the only attack he uses is the Big Gren Lasery Move(sorry, I dont know a better name...) And since him doing that means he is Completely concealed...He is all but Invincible...