Maybe it is a known thing for all of you...but for me it was new :)
Yesterday I played against Spite and found out his Kriptonite! Indeed he was beating the hell out of us and his last drug entered (Upsilon something: the one that removes ongoing cards from play and takes them back into hand).
We (Haka, Expatriette and Bunker) were down to 1 digit HPs, but Haka played the ground pond (an ongoing that does not allow non-heroes to do damage until next turn). All of our heroes can freely strike Spite, environment comes (no damage from there either), and we start again: Spite he has many actions that allow him to do damage, but they are all cancelled due to Ground Pond, then he sends back Haka's ongoing (plus a bullet that Expatriette can play for free), and it is heroes' turn. In all, we locked him down unable to do nothing. Haka had his mere and Dominion, so he was drawing 3 cards per turn (more than enough to pay for Ground Pond).
If anyone wants to get his achievements with Spite I recommend Haka!
You need Sub-Zero Atmosphere to make the lock complete, because a lot of Spite's damage happens at the end of turn, where the Ongoing bouncing happens at the start of Spite's turn.
Apostate has 5 cards in his deck that can break Mistform, and 3 that damage every Hero Target, so that still relies on others to do the heavy lifting of actually defeating him.
Katsue's comment hits on the crux of the issue. PL531 Compound Upsilon returns cards to hero hands at the beginning of Spite's turn. Spite does his damage in the middle of his turn ("When he would draw a card") and the end of the turn (Mind-Phyre and Demon's Kiss). So if you return Ground Pound to your hand at the beginning of the turn, it does not protect your guys from damage. It does protect you from environment and power damage, though.
Even Katsue's solution doesn't completely solve the problem. Again, some of the damage always happens in the middle of the turn, and the rest of it relies on the order in which the drugs appear.
There are, however, a lot of ways to completely ruin Spite's assault. Multiple Stun Bolts, general tanking, double-Twist the Ether, Smoke Bombs, armor, and ways far more creative that are too numerous to count, it's not hard to stop him, because you know what he will do every turn. In general, I find it fairly easy to beat him. Here's a link to my guide with an eerily similar title. You'll find some tips I find helpful to dominate him every game.
Oh man, remember pre-nerf Wraith with double Stun Bolts against Spite? He literally couldn't do anything. Just sat there bouncing your stuff back to hand and waiting to die.
Yeah, I was doing something similar with Bloody Knuckles... not a shutdown but basically it boosted Mr. Fixer and then returned harmlessly to his hands. Spite woke up a week later covered in wrench marks.