Absolute Virtue - Hardest Boss in FFXI. No one beat him yet.

They do fixed damage that's true, and that damage could be upped by adding the fixed damage of each ammunition type. But as Strength has no effect on Damage, so does enemy defense. Enemy Defense is completely over-ruled when taking in consideration attacks from Guns.

So at 50 Damage + 4 (from Dark Shot), you'd have a 54 fixed damage, dealing up to 5K. Also, since ammunition also added elemental or status effects, you could play around with the enemy weaknesses, boosting that damage to 9999.

Considering that it's range is also formidable, you could have a party of three Fomalhaut users separated between long distances from one another, which can pretty much limit the damage capacity of most of the powerful marks/monsters/bosses in the game, since most of their powerful attacks are AoE. 

Spider Guardian and Boost Guardian from Metroid Prime 2 (hard mode)

Alma from Ninja Gaiden on Xbox. I never did beat her though.

I tend to forget how hard something was, but most frustration I had was Seth in SFIV, he is super cheap fucking bastard and how many times I had to replay it on normal for trophy... And Hades / Zeus fight in GoW3 from my recent memory, while Hades was hard (but good), Zeus fas fkin annoying that last stage took me like 20 tryies and since it takes like 5 minutes to finish I was seriously super pissed off.

And don´t forget Death Penalty glitch.

Anyway, for topic. Demi-fiend frod Digital Devil Saga and Satan from Digital Devil saga II. You must have best characters, have púerfect strategy, know precisely what to do a what not to do. And still, if you have bad luck, you die.

The 2 hardest bosses I ever fought in a game was ARES on the hardest difficulty in GOW1 and Radec on elite difficulty in Killzone 2

Sephiroth in Kingdom Hearts 2 and Vanguard in the tutorial level of Demons Souls!!
Both are close to impossible.

Alma's bitch ass in Ninja Gaiden. No boss will ever be as hard as she was. I'm a skilled gamer, too. Trust me, she's the hardest boss ever.

Alma isn't even the hardest boss in the game

Tutorial Vanguard is quite easy if you are proficient at dodging, as you need to get out of the way from his first two swings and position yourself in an Southwestern position near his left leg.

This will cause a glitch in the Vanguard AI, and the only move he'll ever use is the Flying butt stomp which is fairly easy to dodge. Just kept hitting him, whenever you see him fly, get away, and when he hits the ground immediatly go back to hit him. I've killed him with pretty much every class using this, even the painstakingly slow Temple Knight.