This could quickly turn into a Mr. Fixer breaks the world thread, so for a change up (all credit to LewdDolphin for this one): Throat Jab + Wrest the Mind.
Throat Jab Visionary and have her drop Wrest the Mind on say, I don't know, an EPE from Omnitron and suddenly you've got a 75 (5 player game) point nuke going straight at Omnitron. Drop it on an Explosives Wagon enhanced by a couple of Skyscraper's Aggression Modulators for even more fun.
It seems a lot of our great combinations requires heros beating themselves up. That's kind of sad, pain is good?
In fairness, the Throat Jab & Wrest the Mind trick came from a video I saw a year or so ago (it might've been Nunleft speedrunning Omnitron) which did involve Wresting the EPE's Mind with a Throat Jabbed Visionary :P.
Actually I was wrong! It was apparently Darklyte from March 2015, though he used Divine Sacrifice on Visionary instead of Throat Jab… https://www.youtube.com/watch?v=0Rmh03LGW_k
Hey, lots of comics have the heroes pulling off extraordinary feats by overdoing it and doing some kind of damage to themselves, so why should SOTM be any different?
But just as a mental exercise, I have concluded that Captain cosmic and Sky-Scraper are Mr. Fixer's best friends.
CC has three each of Augmented Ally and Cosmic Weapon and all of Sky-Scraper's Links can stack. That means with Jackhandle, Grease-Monkey Fist and Harmony, you can have as many as seven AOE attacks in one turn (Three CWs, Overdrive or Charge, then the two from Cortex Overstimulator), all at +2 except the first blow.
Oh yeah, Fastball Specials, Arrow Special (Hawkeye firing Ant-Man who turns to Giant-Man) Just, realistically, silly to beat your friends up for victory! HAHA, I'm just making a dumb observation.
On the flip side, I played a game against Advanced Bomber Blade today where my primary means of attack was “tricking” Blade into hitting himself and triggering the 2 Backlash Fields he had in play… It was a pretty great game (and a strategy I’d never used before).
If, for some odd reason, the villain is still around after this, Visionary can also cocoon up on her next turn to keep it going. 
So great!
Heroic Infinitor, Dr Tremata, and Tony Taurus are best friends until Infinitor loses it again. Since Heroic Infinitor counts as a hero target on the initial side he can't damage either one of them. Once he flips though they better run.
Even more, if you have Sky-Scraper drop a couple of Compulsion Canisters on him, and that will all be irreducible!
Everyone knows the best combo is Guise borrowing Jackhandle, High-fiving Absolute Zero and then using Thermal Shockwave. Preferably with Barbarian in play.
That's a fun one if you can pull it off.
Akash in The Block vs. Guise, AZ, Fixer, XPW Fanatic and Grandpa Legacy.
Block plays riot, tons of targets for akash and environment.
Guise borrows Jackhandle, plays Uh Yeah on AZ, uses I can do that too to copy Fanatic's innate power, then Grandpa Legacy lets Guise use Thermal Shockwave.
Akash took 7 shots of 2 cold damage (Inspiring Presence) 3 times, then fell on #4 of 7 hits of 42 fire damage.
I mean, we set the game up hoping to pull it off, and it happened.
Can't wait till XPW Fanatic is in the video game.
Put Twist the Ether on Guise and change everything to cold damage.
GLHF
GLHF?
Guise Laughs, Heroes Frown
(Good Luck Have Fun)
One I just discovered -- Fixed Point is NASTY on Vengeance. Not only do all the Villains continue to have full turns despite negative HP, but Proletariat with a single Clone out is practically invincible as all the damage gets redirected to a clone even with the clone at negative HP.
This is awesome, and I need to try it.
That said, I will never try this outside of the Video Game without an assload of counters in front of me.
[quote="phantaskippy"]
Akash in The Block vs. Guise, AZ, Fixer, XPW Fanatic and Grandpa Legacy.Block plays riot, tons of targets for akash and environment.Guise borrows Jackhandle, plays Uh Yeah on AZ, uses I can do that too to copy Fanatic's innate power, then Grandpa Legacy lets Guise use Thermal Shockwave.Akash took 7 shots of 2 cold damage (Inspiring Presence) 3 times, then fell on #4 of 7 hits of 42 fire damage. I mean, we set the game up hoping to pull it off, and it happened. Can't wait till XPW Fanatic is in the video game.
[/quote]
Did a hero close to this but in my case Akash'Bhuta has gone through a whole chain of Primeval Eruptions so most of her limbs were out. The resulting fire damage was 107 to each target. Since I had Super Ultra Kawaii!! in play I had Guise the Barbarian and X-Tremeeeeee!! out before the power use.