This is a great game and I know that. Everyone tells me that. It's the grand-daddy of some of my favorite games.

I hate this game. I don't know why but nothing hits for me. I dislike the art style, the grossness, the humor, and the themes aren't doing anything for me.
That just leaves me with a game that controls clunkily (Intentionally I believe for the theme), looks ugly and doesn't tell me what any item actually does, making trying to make builds incredibly difficult. That's an issue when building power based on your power ups is kind of the core of these kinds of games.
I've been told that specific complaint gets solved by mods, and that this game should always be played with those mods, BUT to me that's an indictment on the game itself for not having these basic features.

Full disclosure, I played Enter the Gungeon long before getting to this game, and by the time I reached Isaac, it felt like a massive downgrade in absolutely every way from Gungeon and left me wondering why people rave about this game so much.

TL DR: This game must be good for so many people to think so, and it inspired so many games I love, but it is clearly not for me.