Cain can only shoot tears from his right eye. This affects certain items: Blood Clot and Chemical Peel have a 50% chance to do increased damage and Technology 2 will prevent him from firing normal tears, even tear-changing effects like Brimstone. Also, the R U a Wizard? pill will cause Cain to fire tears to his right exclusively.
Cain starts with slightly higher damage and speed than most characters, making him more agile and effective at the start. However, he has lower range and health than average, which means he has to put himself closer to danger and can take less punishment than most.
As mentioned above, Cain only shoots tears from his right eye. This makes it easier to aim as him, and lets Cain consistently peek around corners to shoot behind cover.
Lucky Foot changes stat-changing bad pills into good pills, making pills extremely effective for Cain. This makes Golden Pills and Echo Chamber great finds for Cain, as you will receive multiple guaranteed buffs from the pill.
Cain's starting key guarantees that he can spend it on opening a locked room (eg. Treasure Room) past Floor 1, or a Locked Chest. If Paper Clip is unlocked, Cain can unlock every golden chest he finds, which significantly increases the chance for an item or a mass collection of pickups.
Cain's luck makes him a good candidate for tear effects, as many of them are more likely to trigger based on luck.
As he starts with only two hearts, Cain benefits from early health ups, and is not a very good candidate for Devil Rooms early on since they will significantly cut his endurance.
As Cain is likely to have a large collection of coins or keys after a few floors, it is wise to open up Shops, bomb Shopkeepers, donate ten coins to a Donation Machine, or donate to a Beggar till he pays out to maximize the chances of an Angel Room. Cain benefits more from them compared to Devil Rooms due to his low health.
Abel's tears become red and deal 7.5 damage when held by Cain.