Story said:
I'd say Ballos, since he's the only boss that I've never beaten. The closest I've ever come is about 2/3rd of the first form. I just don't get it, since everyone else makes it look so easy.
(I've got MG, Nemesis, and maxed out HP and Super Rockets in case you were wondering.)
There's a trick to it.
When he charges (he screws up his face right before charging, so that's the cue) do a long jump over him. He'll fly at you, so run to the left. Do a high jump over the fireball and bone spray (a classic mistake is to be running away from Ballos and jump in the same direction the fireball's going - this basically ensures you get hit). You only need a distance of about half a screen between yourself and Ballos to ensure that you'll be able to clear him.
When he flies into the sky (which he does after every four charges), run back and forth under him, trying to keep the direction change for a point when a crosshair appears. You won't get hit that way. It'll probably take a few goes to get the rhythm down.
His final attack is to lay down lightning bolts across the whole screen. Stand betweem two crosshairs and you'll be fine.
The safest times to hit him are 1) between his charges, when he's resting, and 2) when he flies up into the sky, before he starts using the lightning (there's quite a pause).
This method allows me to beat his first form with no damage over 50% of the time (occasionally I misjudge a lightning bolt or something).
The second form is a bit of a breather, but requires a tricky maneuver to hurt.
Basically, he jumps at you. Every three impacts, he'll wait for a moment. When he comes down out of the ceiling, that counts as one impact, so he'll pause after only two jumps the first time.
Here's the "safe" way I first beat him with.
First, you have to place him properly. Stand between the two leftmost columns in the Seal Chamber after defeating the first form (there's quite a bit of time between the two forms, so it isn't really an issue to get into position). Once the crosshair appears, move to the right.
When he jumps at you, if he lands on you it does a ginormous 16 damage, so avoid that. It also sends out a fireball which kicks up bones, identical to the first form. Generally, you should try and keep your distance, so that you can concentrate on high-jumping the fireballs, instead of having to also worry about not being crushed.
When he pauses, jump and boost up to the level of his eyeballs and shoot him. Then boost sideways under him when he does his next jump and wait for him to pause again. Repeat until he's dead (without the Spur, I can see this getting exceedingly tedious. The Nemesis should work okay, though, just don't shoot the mooks flying around the top of the screen.).
The third form may seem a little scary, but you just have to keep a cool head.
Basically, he rolls around the room on eight auxiliary eyeballs that he grows. Getting crushed by the eyes when he's on the ground deals 14 damage. He'll also drop a few skulls when he's on the ceiling, and those deal 4 damage.
You have to shoot out all the eyes to move on to the fourth form; when you've done enough damage to an eye, it will close.
When he's on the ceiling, avoid the highly obvious skulls while shooting at the eyes. While the skulls are easy to avoid, be aware that they don't disappear immediately upon hitting the ground, and touching them still deals damage until they do disappear.
When he's on the ground, simply stand between the eyes. Shoot at any open ones.
The shortcut to beating the fourth form is pretty well known (get hurt by the spikes, jump up into the eye socket, spam missiles). Even without using it, all you really have to do is button-mash Curly's Nemesis at Ballos and he'll probably die before you do.