Several years after its original Flash release, The Binding of Isaac is still the top of its genre.

While the themes and aesthetics are certainly divisive (The lead developer, Edmund McMillen, has a preference for the crude and disturbing, as he uses game design as a sort of personal therapy to deal with childhood trauma), and not to my particular taste, you simply cannot argue against gameplay of this caliber.
What Binding of Isaac has, and other games in the genre, like Nuclear Throne, Enter the Gungeon and Risk of Rain, does not posses is a focus on really amazingly pickup interaction. The amount of work that must have gone into making each item work in synergy with almost all other times is amazing, and watching you huge "Brimstone" laser split into four when you pick up "Mutant Spider", and start bouncing off the walls after picking up "Rubber Cement" is simply just so much fun. Sure there are your run-of-the-mill stat upgrades, but they dwarved by the sheer amount of crazy items that will make you completely change your playstyle based on what items you find in a given run!

Any game session usually takes between 25-45 minutes depending on your skill level. The game is hard, but even when getting repeatedly stomped by The Bloat, you will still get lucky once in a while and find a particularly good item combination, making the entire thing worth it. I usually sit down for quick sessions to relax.
To quickly get better at the game I recommend watching Bisnap's video series on the game on Youtube.

If you are unsure which version to pick up, the original flash version gives a very good indication of what you can expect, and Rebirth and the following DLC basically just added a huge amount of new content and item interactions to the game. Rebirth is an objective enhancement of the original, but it might still be worth picking up the first game to check if you enjoy the gameplay before buying the full package.