How do I defeat General Darian?
Darian does not have any special weaknesses, but a trick to know when fighting Darian is how to avoid the SpinBlade Stabbers he uses. If you stand underneath a light, Darian can't use his Stabbers against you. If you do it right, you can blast him through an open door and then scoot out of the way.

How do I defeat Sebastian “Doyle” Krist?
Joe Siegler says:

“... Krist, if he escapes the room, and goes up on a stairwell of GAD's will stay up there, and won't come back down. That's a bug. It was fixed in v1.3 registered, but is cute to see if you don't have v1.3 registered.”

How do I defeat the NME?
Joe Siegler says:

“NME can't fire at you if you land on him, but if you land on top of NME, you're pretty much SOL anyway, since as soon as you jump off, you're hosed.

Oh yeah, don't lead NME out of the room he's in. We never intended for him to leave the room he's in, and if you do, and get him down near the SpinBlades, the game will crash.”

“I have a standard answer for all other bosses besides El Oscuro:

As for the boss creature, there is no trick that I can tell you like ‘move the left arrow five times, hit the up arrow, dance a jig, fire 7 times’. It's really just a timing thing. You need to watch the guy, and see what his pattern is. All Apogee boss creatures have patterns, and if you watch them, you'll see where you can safely go and where you cannot go.”

How do I defeat El Oscuro?
Joe Siegler:

“The trick to El Oscuro in the “Lair of El Oscuro” level is to not fire at him at all. You need to just avoid him for awhile, and he'll eventually expend his own energy and die. Firing at him only makes him stronger.

Bear in mind that this is not the last level, there are two more levels with some variant of El Oscuro.”

How do I defeat Snake Oscuro?
Joe Siegler says:

“Here's how to really do it. (This solution implies that you save your game several times, since you'll probably die a few times doing all this if you've never done it before).

To defeat El Oscuro properly in the “In the Dark Nest” level, you need to first get rid of the two rooms of larvae that are at the start of the level. Do NOT go up the stairs right away. Back up, and get one of the heat vests, and look around on the left hand wall. There's a bunch of larvae in there. Destroy them, and while you're in there, go over towards the Oscuro wall, and you'll hit a touchplate. Then, go back to the stairwell, but do not go up, go into the similar room of larvae on the other side, and you'll note that a wall has moved back, and you'll be able to get the Oscuro key behind a wall that was in the way (it would have been in the way if you went to this room first). Get rid of all the larvae in this room too, and THEN you can go up the stairwell (you might as well grab a fully charged weapon and another heat vest before you go up there).

Go to the top of the stairs, but do not go over yet. Look down, and you'll see two “rooms” in front of you. The rightmost one is the one you want to go at first. If you just walk off gently, you'll fall on a mercury mode that is suspended in the air. If you run off, you'll miss it. There's a touchplate around the outside of the aforementioned “room” that will allow access inside. (This goes for all 4 “rooms” in the main battle chamber, but this one is the one we want to concern ourselves with now). Anyway, inside there is a touchplate. Hit that touchplate and a firewall at the far end of the room will move out of the way, revealing a doorway which is opened with the Oscuro key you got before you came up the stairs. To get over the wall, you need to do one of these things.

Try not to let Snake Oscuro get trapped in here with you, or it will make things very difficult.

1) Fly over it (if you got the mercury mode when falling off the steps).

2) Grab the firevest, and then the firebomb. Turn around, and point the firebomb at the floor. You'll fly up in the air, and over the wall.

Once over, there's a pushwall to be pushed. Follow the now opened up pathway, and you'll be led to the third room of larvae. Look out in this room, as there are a lot of Deathfire Monks in here, too. Once you dispose of all the larvae, SAVE YOUR GAME! :) You can then go back out the way you came in, and defeat the Oscuro Snake, and on to final victory.

Note: The Oscuro snake can only be hurt when he's over a firepit.”