Since the AI is inept at any targeted powers the most effective characters are those with annoying passives or devastating one-shots if they’re allowed to gather the AP.
Cage & Fist - these are the top two I see on defense, given their annoying passives. Cage nullifies match damage unless you’re getting hit by 5*s, while IF guarantees your opponent damage they’ll either have to heal up or risk in their next fight.
KK - highly annoying, IF paired with characters who have low-cost abilities. If her partners’ lowest power is 9 ap the chances of her healing anything are slim.
Hood - Though extremely squishy, his AP steal can delay plans, possibly shutting your opponent down if they draw an unforgiving board.
Blade - I’ve been trounced by Blade a few times. If there’s enough red he’ll fill the board with strike tiles, and unless you’ve brought along someone who can punch big holes in the board, it can build up to over a thousand damage for a single match.
Magneto - his yellow bombards the board with protect tiles. It’s not particularly cheap, but once he gets one out it’s a rough road to being damage-positive. He often has enough time to collect enough to fire again just after you’ve whittled it down to 2-3 tiles.
I generally focus on one of those and then look for synergy. Cage/Fist together give you four non-overlapping powers, but none of them are all that synergistic - Cage will steal the black with a weak punch, stopping fist from firing off cheap purple bombs and double the strike tiles. The individual automatic tiles are annoying, but their active powers neutralize their offense.
My favorite (in simulator, at least), is focused on KK. I pair her with Gamora and She-Hulk. Both of them have cheap powers that activate KK’s heal. The overlaps are green, (which She-Hulk will steal to drain opponents’ AP - devastating if it hits the color(s) your opponent was trying to build) and red (no ground pound for She-Hulk, but a 5AP swipe that triggers a heal is decent).
I’ve also used Vision/Blade/Fist a few times. It’s not as effective on defense because Vision will often overwrite his own countdown with the other power, but if he does manage to get density in play, he’s got great damage potential since he tanks all three of his colors. Blade and IF are doing their own annoying things in the meantime, but like Cage/Fist they nullify each other - Blade won’t get enough purple to fire attack tiles since IF will use them to make black, and IF won’t ever have enough black to upgrade his powers since Blade will consume it swinging his ninja sword like a baseball bat.
It really is a well-balanced tier. Most complimentary synergies come at the cost of nullifying a partner’s more effective ability.