I have like 500 hours in Isaac and started playing Rebirth in 2014. I have 600 hours in Slay the Spire, which I bought last year. It's my favorite roguelite of all time, and one of the most well designed games I have ever seen. Compared to Isaac, it feels so much more fresh, the synergies are way more intricate, and the game doesn't start getting fun only if you get a damage upgrade early. The characters play differently as well. Isaac is not bad, but it has a few design quirks that can be annoying, such as the absolute plethora of useless items.
Funnily enough, I never got much into Spelunky because it's one of the more repetitive roguelites for me: the flowchart of killing the shopkeeper, going to the hidden market and sacrificing to Kali means that every run is basically you with a shotgun and a jetpack/cape flying around the map safely and saving bombs for the basic final boss. Wish the game had more items and viable strategies.