It seems that Binding of Isaac supports joypad, but simply connecting XBox 360 joypad does not work. Do you know how to setup it?
To say that the Binding of Isaac supports the use of a gamepad would be a slight exaggeration.
The latest patch for the game added control options to the game, which looks like this:
And as you can see, the game specifically tells you to use one of the many gamepad to keyboard solutions out there, specifically JoyToKey. This thread describes the alternative of using ControlMK, with specific instructions and even a ready-made setup profile for the game (though I can't vouch for its quality as I have never tried it). The thread also mentions Xpadder, as per Kalamane's answer.
I personally use the DS3 tool and a Dualshock 3 (I actually prefer the keyboard, but my keyboard has some key-locking issues so I can't walk diagonally and shoot right at the same time).
This review says Binding of Isaac lacks gamepad support.
However, if you still want to use your XBOX controller, you should download Xpadder. It's a free program that lets you map keys and other inputs (like the mouse) to buttons and thumbsticks. You'll be able to configure the XBOX controller however you want.
You can use this for any PC game, even if it doesn't have native support for gamepads.
How to setup a joypad for Binding of Isaac
Download Xpadder- http://www.softpedia.com/dyn-postdownload.php?p=45445&t=4&i=1 Recommended Settings:
w, a, s, d - Move up, left, down or right. Set to Directional Pad and L3.
↑, ←, ↓, → - Shoot up, left, down or right. Set to R3 and 4 buttons.
space - Use current activated item.Set to R1.
shift, e - Set to L2 and R2.
q - Use single use item, either a tarot card or a pill. Set to L1
p - Pause the game. Note that when paused, p resumes while esc offers to quit. Set to Start.
f - Toggle fullscreen. Set to Back/Select.
On OS X, I've had success with Enjoy.
To set it up, press the gamepad button you wish to assign, then select the key you want to assign it to. Press the "Start" button in the toolbar to make the button presses emit keystrokes.