If it's any help, I did both lose to and beat infinitor before unlocking him
Maybe try this with no incaps, and having lost to him once?
I've done it without incaps and CC not in the lead. I don't think I've lost yet.
There could also have to be a certain number of consturcts in play. Here's the screenshot for when I unlocked him.
I also had the following before or during the match:
There were about 8 consturcts out (Legacy had one or two)
I have defeated Infinitor before
I had lost to Infinitor before
Autonomous blade killed him
Autonomous blade was NOT on Cosmic
He did not flip at all (although I know some people got him even if he flipped)
Has there been a game where a construct DIDN'T cause the final blow?
Also, something to think about is the number of constructs out compared to the number of manifestations...
Edit: I'm guessing there needs to be more constructs out than manifestations?
Lost one and then won without anyone incapped. CC in the lead. Autonomous Blade on Fixer dealt the final blow. Unlocked.
When I unlocked him on stream earlier tonight (video), I had played Infinitor a grand total of twice. Once on Wednesday before his unlock was available which I won with 2 characters incapped, but before his unlock was available, and once on stream where I had Mr. Fixer as the last hero deal the final damage via an Autonomous Blade. Here's my theory:
Defeat Infinitor via damage from a Construct. No hero can be incapacitated, and Captain Cosmic must be in the lead.
Apparently CC does not need to be in the lead.
At the time I unlocked him, I hadn't lost to any Wrath villains yet, so losing to Infinitor in a previous game is not a prerequisite.
I had several constructs out, but I don't recall which ones or how many exactly, since I wasn't actively trying to unlock him.
Also, after double-checking the unlock screenshot, I realized that I won on the environment turn, probably with a combination of Wrest the Mind on Orbo damaging Visionary leading to Dynamic Siphon activating Cosmic Weapon, which triggered Autonomous Blade, finishing Infinitor.
Edited after rechecking the screenshot.
Beat Infinitor for the first time. Final damage from a Construct is not a thing. Or if it is, it can't be from a hero that is not Cosmic. Oh and he was in the lead of my team
Maybe a specific manifestation or group of manifestations have to be destroyed? Can people record which manifestations they've seen?
I'm pretty sure when I beat him in that game he had every manifistation in play at one time. He even reshuffled his deck. The only one he had in play when I beat him was Miscreation.
That could be the case. I ran into every manifestation at least once, and when I killed him the only manifestation out was a twisted miscreation
Just unlocked with Autonumous Blade dealing the final damage, from Legacy, CC leading.
Also, Infinitor only had one manifestation out, maybe he can't have more than one in play when incapped?
So my guess is:
Beat Infinitor, with Captian Cosmic at the head of your party. The final blow must be from a construct and there must be only one manifestaion in play.
No unlock.
Five heroes out, Captain Cosmic was not the head, no manifestations in play, Autonomous Blade kill off of Chrono-Ranger.
Legacy, Omnitron-X, Captain Cosmic, Chrono-Ranger, SS Tachyon was the order.
Did you not read my last post. Those are the exact specs I had when I beat him and it didn't unlock. 
Same thing (same team, no manifestations, Autonomous off of Chrono), except CC put in front: Unlocked
(the first was my first fight; the second was my second)
Telling me the condition is likely:
With Captain Cosmic leading the team, defeat Infinitor using the damage from a Construct.
Or a permutation thereof. with no incapacitated heroes, or after every kind of manifestation has played at least once, or not on the heroes turn (both of mine were during villain; someone else stated during environment?)
There were two Manifestations in play when I unlocked.
How many Constructs did you have in play when you struck the final blow?
Dunno. At least one. No more than seventy.