After playing against GloomSpite several times, I've discovered some interesting things but also have some questions.
Victims seem to be a trap, oddly enough. Unless he plays victims and only victims, it's not really worth it to even attempt to flip him. Each time he plays a non-victim card, it gets harder and harder to flip him before he's got his full loadout. But once he DOES have a full loadout, flipping him only makes him hit harder. Collateral Damage is the worst because it doesn't play a new victim like On the Prowl does, plus he's likely to kill a second victim with his end-of-turn attack. Deck Manipulation is key for this route, and since he only ever plays one card a turn deck manipulation is quite easy. Otherwise, it's best just to leave the victims to their fates.
That said, his backside is so horrible that I find it simpler to just fight him on his frontside. He deals substantially less damage, he hits the highest target instead of the lowest, and when he kills a victim all he does is heal himself. One Collateral Damage chain on his backside is all it takes to turn the tables against the heroes. It seems best to eject everyone but Thiago from the safehouse as soon as possible to get his damage under control. Not only does this prevent chaining Collateral Damage, you get extra card plays that can really help against PL531. We only put Innocent Bystanders into the safehouse on his backside, and only so we can immediately eject them again.
Another thing that's interesting is how differently he plays with different numbers of heroes. Unless H=5, it's not normally possible to actually turn any of his drugs facedown. Even if H=5, you need at least one Good Samaritan (or Omnitron-X's Timeshift), and EVERY card Spite plays must be a victim. Otherwise he'll flip before he turns anything facedown. The only way to turn drugs facedown with H=4 is if Spite plays a victim on the first villain turn, Timeshift plays a victim on O-X's first turn, and you can save all three of them before the second villain turn. If you can miraculously get ahead of the drugs, Spite becomes a total pushover (at least until Forced Entry). You'll be fighting his weak frontside with all the benefits of fewer drugs. With H=3, though, it's much much easier to flip him before he gets all his drugs out, and when you do flip him, the first turn is a lot less terrible since he'll have at most a +4 damage boost.
Because of all these reasons, we generally don't even bother saving victims at all unless we start with two victims, or we start with a Good Samaritan and have deck manipulation in hand. We just let Spite get his drugs out one at a time, and we burn him down as fast as we can without flipping him. Since he doesn't heal himself except when he kills a victim, he goes down MUCH faster than regular Spite. Keeping everyone outside has the added bonus of making Thiago stick around a lot longer than with normal Spite. GloomSpite only plays one card a turn, so it's usually a lot easier to reliably keep him alive. He's often spent the first half of the game hanging out in the victim entourage and the second half alone in the safehouse.
I do have some questions. Are we the players supposed to know which of the facedown drugs are which at the start of the game? The setup instructions don't say anything about mixing or randomizing the drugs. Do you prefer to pick a particular drug order, or do you shuffle them and let fate decide?
Additionally, there seem to be some potential quandaries regarding the victims. Unlike normal Spite, there's often little mechanical reason to actually save the victims. In many cases, saving a victim will make it much more difficult to actually defeat GloomSpite. Does this bother anyone from a moral or design standpoint? With regular Spite our group often agonizes over whether to save a particular victim and whether we can actually keep them safe from Forced Entry. With GloomSpite we only save them if there's a clear benefit to be gained. We'll often even personally eject them from the safehouse onto the streets for our own benefit. Does this make US villains as well?