So right off the bat I want to say that this is a very fun game. It has an aggressive rhytm, you never know when one of those yellow things is gonna pop up and take 3 HP of you at once. That's what gave earlier video games purpose, they were unforgiving both with enemies and game overs (you start all over, here) and what is ultimately responsible for the success of Binding of Isaac. The collectables feel rewarding and push you deeper into the game.
The soundtrack, though so far in my playthrough composed only of 2 tracks, hasn't really grown stale. It is very enthusiatic and vibrant, and couples well with the art style that the game is composed in. Story is very straightforward, but effective in making you feel like you have something to lose by losing. The fact that if you rocket jump in Heaven outside of the initial area you can see some interesting stuff and that you can blow off signs shows polish to minor details.
Your own bombs don't hurt you, and this is well thought-out, as in some parts of the experience you won't have a lot of space to run away from your bomb while attacking something. Not a lot to say about that, but it is absolutely essential. There's a diversity of environments, from deserts to forests, but that doesn't really impact the enemies in any way and if it did it would very much booster replayability. It still is refreshing, because it gives you new objects to blow up, such as flowers.
The only quarrels I have with this game is first and foremost that it needs to be visually more consistent. The pixel art in the actual gameplay conflicts with the more cartoonish HP meter, scoreboard and etc. Second, the game throws you into it without really explaining how the controls work and how do you plant a bomb, forcing you to go into the options menu to see that. I get that Z and X to interact with the environment is standard in itch.io games but it affects the acessibility and potential popularity.
But perhaps the most detrimental aspect in gameplay is the camera disobeying you if you want to go up. A lot of the time you will want to get some collectables you lost or protect yourself from a sudden attack, but that will be impossible. Going up is more relevant than I think devs have realized. But I can also see complete freedom with the camera making the game less forceful and challenging, so a middle ground is needed here.
A very minor problem, because the controls are pretty great and fluid, I never had problems with that and it adds to the fast-paced experience. However, changing binding controls should be more effective. It is pretty time wasteful if you want to change a single key to sit confirming that you don't want to change all the other ones.
tl; dr Very enjoyable and well-executed game, definitely not perfect but not far from that.