Generally, I think Legacy, Argent Adept, Visionary, random damage dealer, makes a great team.
I'm not saying every team needs to have her, but if we're talking about 1 team of four that you could take up to any villain and feel confident with your chances, I have a hard time leaving TLT out. The more I think about it, the more I think TLT, Grandpappy Legacy, Dark Visionary, and any Wraith would be my top four. (How interesting of a project would THAT be for a lengthy series of solo games? Take the same 4 heroes and cycle through all the villains to see if you can go undefeated. Since we're talking about getting the best heroes, I think using the hardest environment [Rook City] every time would be the way to go as well.)
Agree 1000%. This comes out even more when trying to think about bad combos, because just about everybody has some sort of synergy, DR, support, or whatever to help the team as a whole.
But it's still fun to discuss top four 
I had a crazy random last night. TL Tachyon, Bunker EoW, Legacy and The Scholar vs Omni in Time Portal. It was a complete one sided fight until the computer room pulled the Electro-Pulse Explosive right before the villain turn so it went off before any damage could be done to it.... 15 per hero across the board knocked everyone near single digits. No deaths of heroes and Scholar was almost full again at the end. Just a rout. Pretty overpowered team though I imagine any team with TLT and Legacy would be.
One of my favorite teams is Legacy, Ra, Argent Adept, and Fanatic.
The damage output of this team out of the gate is silly. With Argent on saraband duty whenever needed, nothing could possibly live long enough on the board to do much. The only downside to this team is trying to figure out who to give embolden to.
Also, any team with OmiX and Tempest. Sheilding Winds is the greatest card anyone could play for OmiX
Shielding Winds only works if you're taking a single, 5+ damage hit. If the damage is coming bit by bit (eg from Thugs), it sadly won't help much :(.
The best 4-player team, imo, are the 4 in whatever game I'm currently in.
The ultimate team:
Legacy, Team Leader Tachyon, Dark Visionary, and Omnitron-X. I can't think of a situation they can't handle, and they are all great by themselves, and the combos are amazing. Lead From the Front almost guarantees no components are destroyed is just one of the many broken combos I can think of.
Guarantees it? Never had a Kraken pop out and put Omni-X in a head lock while he was doning his Elemental Exochassis before?
That's a pretty specific corner case. I'll grant you that you do have to worry about the environment, but only about half the environments have a card that can do 5 damage in a turn and even then there are plenty of targets other than Omintronks that may get hit. Besides, I prefer using Dark Visionary's power on the environment over the villain deck. Still you are right it's not a guarantee. I'll edit it.
Here's another one: Dark Visionary's power is awesome. But anyone that has used it or Infrared Eyepiece knows that every now and then you'll stumble across two copies of the exact card you were trying to avoid. Then there's no way to stop it. Or is there? Omintron can use his power to reveal that top card and then trash it.
There is. Utility Belt and 2 Infrared Eyepiece.
Personally, I find that the best 4 player teams are those that compliment each other. In all honesty, I think >G pretty much spelled it out on the front cover of the EE box with Legacy, Tachyon, Bunker, Wraith, and AZ. Now of those five, I usually have this set up:
Finest Legacy as my first pick due to the fact he is versitile enough to either attack, heal, or buff all of the heroes. If it is a middle ground villain, I may use Young Legacy instead
Tachyon as my second due to being able to potentially draw many cards and play many cards to do little bits of damage and build her burst pile. Team Leader Tachyon is slowly becoming my favorite to use for power use alone as sometimes you just need that extra card.
The Wraith is usually my third pick because she has versatility to pick up where either Legacy leaves off or potentially do a ton of damage from her projectile weapons. The Price of Freedom Wraith is a good one to have if you are fighting villains who switch immunity to certain types of damage to have more than one option.
Finally either Bunker or Absolute Zero. Bunker is one of my favorites just because he can do allot of damage especially from his omnicannon, but AZ has the ability to really do some damage to himself, heal himself, and cause massive damage to everything in play.
So when in doubt go with the Freedom Five, but as always, play whom you want to play as and build a strategy with them. Sometimes you get annihilated and sometimes you just overpower the villains. Remember that this is comic book based, so sometimes you win and sometimes you lose, but keep on fighting.