As always, take a deep breath. It's gonna be okay. I'm gonna get you through this. PKB has your back.
This is not intended to be a Spec Op 6 specific guide. This is intended to be a general guide that you could apply to Spec 6 (and 7 and 8 and however long this nonsense goes on). But, since I only have 6 to work with at this time...
There are no comic covers that are rarer than others. They are all equally weighted. Good news, bad news. The good news is multiple. First, it makes the math easier. Second: No Rares! But the bad news is that you could open a thousand crates, or even ten thousand, and never get the 8th item. It is possible they have put some sort of stop loss in there and I'm too dumb to see it. I wouldn't put that out of the realm of the possible, because reading XML is not anything I do as more than a very casual hobby.
All normal bosses have a 15% chance of dropping Lockboxes. 10% for 3 and 5% for 5, making a 5 lockbox = to 5 CP (funny, because the lockboxes are worth twice the gold), 20 UISO (also worth less than half of the lockboxes), and the item drop. The epic bosses, on the other hand, present the 12 Lockbox combo as a 5% drop, the 5 box as a 9% drop and the 3 box at 15%. Yes, that is a 29% chance at some quantity of lock boxes on the epic run.
So, a wee bit of math. Your expected return on the regular roulettes (Dragoness, Mystique, Monolith) is .55 Lockboxes. UGH. Your expected return on an epic roulette is 1.5 Lockboxes. So, an epic run is worth 2.05 Lockboxes. I think the path is clear there. Which epic boss to run? Well, they cost the same number of UISO, but I will tell you this, the Green Goblin is the single best roulette ever offered in the game with a higher return on CPs than normal roulettes (55%, expected value of 2.4 per spin, versus 2.25 on normal epics (and the Living Pharaoh epic), and an 89% positive outcome (CP, lockbox, or OsCorp Prototype).
How to Open
I got beaten to the punch, very badly. Wearingglasses has produced an excellent blog on the math behind the lockboxes. You should open 10 at a time if you need comic covers. If you have already recruited Magneto, you should open them one at a time, to reduce your chance of getting covers and thereby increase your odds of everything else. I am not sure if this increases your odds of past epic drops, but it does not hurt to try.
Still To Come
Box Odds. I'm working on it, but they seem to have hidden it well.