NOTE: These screenshots show the single-player game. In the co-op game the mirror puzzles are exactly the same, but you can use your characters to depress the pressure pads instead of moving balls around.
Start by fighting off various regular and fire scarabs and avoiding Apep's spitfire as you work on destroying the first 2 Marks of Set.
Note that the mirrors will protect you from the spitfire if you stand on the pad behind them.
There are 4 square pressure pads, but only one of them will raise the mirror that you need. So roll the metal ball onto the pad between the 2 Marks. (Again, this may be the left, right, near, or far pad, depending on where the Marks are located. See the previous set of screenshots for details.)
Then stand near one of the mirrors diagonally opposite the one that is raised. Shoot a beam from the Staff of Osiris through the first Mark at the mirror. It should then reflect off the mirror and hit the second Mark...
...destroying both and taking a third of the boss's health.
Now fight off more minions—scarabs and skeletons of various types—while avoiding Apep's spitfire until the next group of Marks appear. The skeletons with shields can be hard to hit. Either shoot them from behind or use remote bombs to damage them and throw them off balance so you can finish them. You'll find health packs and ammo boxes scattered around the room should you require burn salve or bullets.
Soon 4 new Marks of Set appear surrounding the boss and 2 more metal balls drop from the ceiling, so you now have 3 balls. Move the balls onto the nearest 3 pressure pads to raise 3 of the mirrors. (It doesn't matter which ones.)
Before the last Marks appear, you must defeat a giant flaming skeleton which drops down on the left side of the room. If you are attempting the Challenge: Kill a Large Shield Skeleton with Apep's Spitfire, do not shoot or bomb the skeleton.
NOTE: In co-op mode there are several giant skeletons. You only need to destroy one with the spitfire to beat the challenge.
Instead run around Apep, letting the skeleton chase you. Try to position the skeleton between your character and the boss, so that when Apep breathes a gout of spitfire, you can roll out of the way so it hits the skeleton.
Meanwhile, various smaller skeletons appear as well. Shoot/bomb them and then turn your attention back to the big one. It takes a while, but if you're patient and just keep luring the skeleton into Apep's sights, eventually it will be destroyed and you'll earn a MAX HEALTH UPGRADE.
If you are attempting the Challenge: Defeat Apep in Under 3:30, don't waste time trying to defeat the big skeleton indirectly. Attack it aggressively, using remote bombs to stun it so you can then blast it with staff or guns. You must defeat it quickly so you can move on to the next part of the battle.
In the final phase, there are 3 Set's Marks, two surrounding the boss and one off to the side. (As with the first set of Marks, the arrangement may vary, but there will always be 3 Marks with one set away from the others.) Position 2 metal balls on the pressure pads farthest from the Mark that's off on its own. Leave the other 2 mirrors retracted.
Stand near the retracted mirror that is farther from the third Mark. Direct the beam through the nearest Mark so it bounces off the 2 raised mirrors, striking all 3 Marks and destroying them...and Apep.
If you get through the fight in less than 3.5 minutes, you'll receive an amulet: the IRON JEWELED FETISH (Regenerating Ammo).
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