I'll start off with the obvious and then move slightly more obscure as I go. I'll list what I use right now, too.
Obviously Get This
Downfall: It's actually a series of mods that were merged some time ago that were all really good on their own, and then they went and made an entire game mode for it. The only downsides is that Snecko sucks, but doesn't matter as you can play as several Waifu versions of bosses. It's fun and balanced, and kinda hard sometimes!
Game Additions
Shop Mod: Let's you buy the Merchant's Rug and sell potions and relics. It's not the most balanced, but it is fun to allow a new way to advance your game state by investing in the future, so I use it. If you find it breaking too many games (by selling On Pickup relics after getting their effect), avoid the temptation or just don't break the game that way.
Mimic Mod: It's only somewhat fun. The fight can get a little long and tedious, but it does add in some variety into the game if you're into that, and sometimes, it just lets you know you're gonna lose because of how slow your deck is. I actually wish the mimics were a bit harder in a different way than they are, but they use mechanics that aren't as fun to play around instead, but it is fun to be surprised by a mimic.
Infinite Spire: Super broken. Like, actually broken. It's super silly fun, but I think the currency between runs is way too strong. I only recommend if you're wanting to feel extra strong. Completely unbalanced otherwise. You can turn off several of the features, but it basically turns every run into "Do I use my infinite external currency to buy a broken card, and a bunch of relics, or no?"
Replay the Spire: Almost balanced. There's a few aspects that make it kinda broken. But you play this mod for the Hell Engine boss. You ALWAYS play with the Hell Engine boss. It is the BEST BOSS.
Challenge The Spire: Adds Boss Rush, and a bunch of other game modes. It's fun a few times to play it, but it's really hard because I'm bad.
Wandering Minibosses: It's fun, broken, and hard as hell. Think you're doing well? Prepare to get absolutely demolished by a random addition to your fight. It's hard to recommend this mod, but I simultaneously love and hate getting murdered by a miniboss, and beating the boss gives you a stupidly broken bonus. Recommended for more variance in a run. Not recommended for balance.
A Better Third Choice: This one makes your choices a bit harder or easier to think through. Unsure if it's balanced or not, but it's fun to have more choices, and they feel fitting in the game.
Sometimes Causes Problems
The Jungle: It's a whole new act made by a bunch of modders. It's fun, but it feels easier than the normal Act 2 sometimes. It also breaks a few mods sometimes, but so do other mods. I've disabled this one while testing because, while it is fun, I didn't like choosing the Act I went to, because I'd choose the easier one each time.
A bunch of other mods that I'm still testing so I don't fully recommend them.
QoL
Relic Stats: Literally just adds stats.
Colored Map: You can color the tiles. SO HELPFUL.
Colored Powertips: You can color the tooltips. Somewhat helpful at a glance!
SuperFastMode: Turn the speed to 10x as fast. Warning: You realize how slow the base game is when you do this.
Random Character Button: ... Self-explanatory. I like picking randomly.
Highlight Paths: I don't have it, but I should.
Synergy Search: You can look for keywords.
Optimize The Spire: Makes loading the game faster by a lot.
Almost good QoL
Minty Spire: I'd recommend this one, but it has stupid meme shit in it that really ruins the feel of the game. If it had literally only the QoL stuff, I'd recommend it to everyone, but otherwise, the creator has explicitly stated they won't add options in for some really silly meme-y stuff.
Characters That I've Tried And Liked
The Gatherer: I actually don't have her enabled, but she's a fun design for a character. I like what she does.
The Disciple: I'm sad this wasn't in the Downfall mod. It's an ooooold mod, and surprisingly well made. It's a bit unbalanced, but in the harder category, which isn't always a bad thing.
Bard: It's well made, but not my cup of tea. Fun fact, I got in a fight with the creator of this mod because I told him I couldn't read the notes and he told me to learn how to read colors. Still, it's well made.
The Runesmith: I haven't played this one in a while, but she was a lot more balanced than a lot of the characters.
The Construct: Actually a fun character design, but if you find one of its many broken strategies, it can be a bit unbalanced. Or maybe they've fixed it since then, not sure.
I've been slowly adding one mod at a time for a while, and these are the ones that I've landed on being really good, but I haven't added any new ones in a while, so I'll have to mess around with some again.
I was also working on a mod myself, but I kinda get bored a lot and come back every once in a while. I'm currently working on Dual-Class cards (belongs to two classes at once, merging class synergies and identities, and also is colored as both of those cards), as well as adding Buffs that offset the standard list of debuffs (Strong --- Weak, Hardy --- Frail, Protected --- Vulnerable), plus some other things I feel like adding when I think of it, but that will be released whenever I actually get around to it, which is probably never. But, when it's done, I'll let you know, and you can tell me how broken it is and what needs changing.