I wrote up this quick topic on BGG...just copying here for a broader audience :)
Thanks in advance for any replies/discussion!
Gloomweaver in The Tomb of Anubis is one of my favorites. My group has never had much of a challenge with ol' GW, but that combination with zombies and mummies and ancient artifacts all surrounding a dark god make it feel like a pen-and-paper dungeon crawl with super heroes! We always have fun with that set-up. Always.
I tend to find the Tomb of Anubis a pretty good environment anyway, since a lot of the Trial cards always seem to hit villain targets :D. About the only really annoying card in that deck is the Scarab Swarm - 5hp, damage taken reduced by one, heroes can't draw cards.
I had a lot of fun with Akash'Buta in Tomb of Anubis. There's a lot of targets to proc AB's extra plays, so it can get kind of ridiculous. But that's the fun part.
Another fave of mine is Baron Blade on Wagner Mars Base. Thematically, it makes sense because then it's not a suicide run for him, and I like how it gives him a third victory condition.
It's just such a fun environment all-around. I love it thematically, and mechanically there's so much cool stuff crammed into there with the relics, and the nemesis icon on Anubis.
Chairman + Rook City = my most exciting battle.
Great comments guys; thanks so much!
I admit, I am most intrigued by GW in the Tomb…thematically, at the least.
Plus my wife loves zombies…so, there's that, too. 
Again, thank you for all and any replies! Loving this game…
I can tell you that I HATED Voss in Rook City. That town loves reducing damage against villain targets and playing villain cards.
Ambuscade on Insula Primalis - just so thematic, especially when he goes invisible and let's the dinos do their thing.
Just add Haka and you've got a four-part mini I'd love to read.
I thought Akash'buta in the Realm of Discord was a blast. I know that seems like it was meant to be her environment, but it's great!
I play SotM solitaire. Ihaven't yet fought all the villains, but am getting there!
Grand Warlord Voss on the Wagner Mars Base was quite fun. The narrative was exciting. I grew up a Kirby fan and reading the Avengers and Legion of Super-Heroes. The game I played against Voss brought back memories of those comics' galactic tales (Kree/Skrull, Thanos, Darkseid vs LoSH, etc.). I'd played on Wagner before, but had not experienced the self-destruct countdown card. In this game, I pulled it up and was floored with its creativity.
I'm in love with this game for its comic book roots, ability to play solo, strong narrative, and creative design. A big THANK YOU to the designers for creating such a fun experience!