Let me give you a little bible lesson to explain the approach of this game. This game adapted the story of Abraham and Isaac, where Abraham needs to prove his love to god by killing Isaac. But in the end the approach was good enough to prove the love to god. The story in "The Binding of Isaac is very similar. You are in the role of Isaac and your mom got ask by "god" to kill you. So you flee into the basement where your adventure begins. Notice that Christianity isn't taken seriously at all and if you are evangelical you shouldn't consider playing this one, you might be offended. If you are not, you might have a lot of fun with it. Let me now tell you the reasons why.
First Reason: Gameplay!
This is a 2D top-down action adventure game, very similar to a Rougelike. The best comparison you can make is an old school Zelda game ( The Legend of Zelda: A Link to the Past for example ). You proceed from room to room killing enemies and collecting items. Goal is to reach the bottom floor and defeating its boss. There are many different enemies and bosses, each one with its own attack patterns and weakness. To own them you have one simple main attack which is shooting tears. This can be upgraded in a vast variety, it scales from shooting pee to deadly lasers. Upgrades are collected through items and mainly you'll find these in secret rooms. Every floor has one secret room where you pick up a special item. They can be passive and boost your damage or moving speed but also there are usable items. Items that will make you invincible or deal great damage to your foes. The variety on items is so vast that I ended up playing the first times while i got the wiki-page open to search every effect on the items i'd picked up. But the key-feature in this game is that everything is randomly generated. This feature lets every round you play feel fresh and new. Although you can play through the game in under half an hour, you wont get bored. First of all the game is hard, so it will take more than a couple of tries for you to complete it. The Second thing is the more you play it, the more items you'll unlock and the easier it becomes, eventually. This game has this "just one more round" feeling.
This is how you start. The pure naked Isaac you might say, but as you advances...
..you'll look completely different. Cause nearly every item you pick up changes your looks. Some combinations are really ridiculous.
Second Reason: References/Humor!
As i already mentioned religion is a big part of this game. Don't get me wrong, Team Meat just makes fun of it. You fight Satan, the Seven Sins and most of the items have a Christian reference. All of this is so comical displayed that it is hilarious. But not only religion finds its way into the mechanics and visuals of the game there are many references to pop-culture and internet-culture in particular. This game has so much in common with the old Zelda titels and Memes like "Forever Alone" have their part too and i'm sure you'll laugh when you stumble over them. The third thing about this game i find very amusing is the "gross-factor", but i'm sure not all will share my opinion. You shoot with tears, vomit, pee and blood. Poop lies around everywhere, the enemies are deformed and if you pick up the "right" items you'll get deformed too. Surely i find this kind of humor very appealing because deep inside my head i'm a little infant. Or maybe I don't take somethings too seriously and the comical look of this game makes this very easy. The last thing i want to mention are the told story elements. If you enter a new floor a memory of Isaac is shown. He mostly gets humiliated in these scenes and it is so funny. Its an instant reward for you defeating the boss. So if you are not overly uptight or religious you'll laugh a few times for sure.
Third Reason: Replayability!
Randomness plays a big role in The Binding of Isaac. Ever game you play is different than the one before because everything is randomly generated. So you end up fighting different enemies and bosses with other items. Nothing is predictable and it takes a while to see every item in the game. I played over 200 hours and still I didn't unlock every item in the game (Notice: I also have the Expansion "Wrath of the Lamb"). To reach the final boss and see all possible endings, you need to play through a lot of times successfully. Also you unlock different characters which you can also play. There are so many achievements to get and challenges to conquer. If I got stranded on a lonely island this would be one game I want to have!
Fourth Reason: Price!
This must be the game which had the best cost/entertainment ratio I have ever purchased. I got the game including the Expansion for three Euro and played over 200 hours of rewarding gameplay with the occasional laughs. But even if you don't get it through a Steamsale of Humble Bundle, it wont cost you more than 10 bucks.
In Conclusion "The Binding of Isaac" is a must play. Its a funny, addictive and cheap game. Sure it might look weird, but ones you get to know it...