I was first inclined to say Cazador's myself, but there is ONE boss i hate more than even them, Mobidius from Shadows of the damned, Huge amounts of health *played on the hardest difficulity setting* Really annoying shield that you have to shoot a loaded shotgun shot on *Which is really hard as the bloody thing got to reload all the time not to mention that it's hard to hit the fucking Holes in the shield* WHILE he still shoots and attacks you, A single attack takes half of your health or more, The shield *if you can't kill it which i just described being near impossible at least for me* It takes half your health in a nondodge move, He suddently spawns those explody things that take out most of the rooms and is also hard to dodge and nearly every third second he pulls the love interest out from under his cape who dies from ONE shot, So you can't use the machine gun AT ALL..so yeah, You get a pistol and a shotgun to shoot him with, you are denied your most powerfull weapons and he has bullshitty abilities.
If i ever see him again i swear i am going to execute the disc in 7 different fashions to make sure it goes to hell!