even tho I've yet to play with this mod I do have a few suggestions for challenge runs.

og tv challenge: all cards in shops, card rewards and events are replaced with colorless cards (the ones you can buy from the merchent). victory conditions is the beat act 3 or obtain 25 unique/different colorless cards.

bane of all banes challenge: start with cursed key, du-vu doll and tiny chest, all curses obtained are ascender's bane, for every curse in your deck gain 1 max energy. victory condition is to beat act 3 or have a total of 12 ascender's bane in your deck.

grand performance challenge: start with grand finale in your deck, whenever you end your turn shuffle all cards in your discard pile and all non retain cards in your hand into your discard pile. victory condition is either beat act 3 or play the grand finale.

fixed deck size challenge: your starter deck replaced with 10 random class cards (you don't have ascender's bane in your starting deck), start the run with question card, nloth's gift and prayer wheel, whenever you add a card to your deck you must remove a different card in your deck of your choice, card removals from shops and events are replaced with card transforms. victory condition is beat act 3.

I have a kind of wacky challenge I think could be fun with Ironclad

Gimme challenge:
You start with two strikes and two defends, and a bash
Whenever you get a card reward, you cannot skip it, and you get ALL the cards in it.
Whenever you go to a shop, everything is free, except card removal, that cost 2x more and scales by 50 instead of 25 per removal, you can remove any number of times in the shop BUT you HAVE to take all the cards in the shop.
Relics excluded are Busted Crown and Empty Cage
Goal is to beat act 3

@Lucky_Lunge I like portions of your suggestion, but I feel it's too complex overall. I would be down for making a challenge with special rules along the lines of "Card rewards contain 1 less card. Whenever you take a card from a card reward, take ALL options" though, that has potential

RNG deck challenge:
Any character
Starting deck is replaced with all cards that create another random card: Infernal Blade, Distraction, Hello World, White Noise, Creative AI, Foreign Influence, Discovery, Jack of All Trades, Chrysalis, Magnetism, Metamorphosis, Transmutation, maybe Alchemize.
No card rewards but start with more energy (maybe 6 energy) and Unceasing Top (so you can draw cards you generate on turn 1) or Fossilized Helix (so you aren't killed on turn 1)
Goal: Beat Act 3

Defect challenge - Claw 'Em Like You See 'Em

Starting deck - 2x Strike, 2x Defend, 2x Claw, 2x Steam Barrier, Zap, Dualcast
Starting relics - Cracked Core, Unceasing Top
Additional rules - Max hand size is capped at 3
Win condition: Beat Act 3

(alternatively, remove Core, Zap and Dualcast from the starting kit, and instead start with Beam Cells or Go For The Eyes or something)

Originally posted by Lord Raptor Jesus:

Defect challenge - Claw 'Em Like You See 'Em

Starting deck - 2x Strike, 2x Defend, 2x Claw, 2x Steam Barrier, Zap, Dualcast
Starting relics - Cracked Core, Unceasing Top
Additional rules - Max hand size is capped at 3
Win condition: Beat Act 3

(alternatively, remove Core, Zap and Dualcast from the starting kit, and instead start with Beam Cells or Go For The Eyes or something)

Not a bad idea!! I'm not opposed to adding more challenges, but I'm waiting until I have one for each character to keep the count symmetrical (it's currently 5/5/5/5, ideally in an update it would become 6/6/6/6)