u/AppropriateSock3646

• Using the glowing hour glass while in the first room of basement 1 will transport you to home.
• If you somehow manage to spawn monsters in Home in such a way that the doors close, for example with a TM trainer, you can see that Isaac's door has a crack.
• If you blow up the carpet in Isaac's room, there's no trapdoor, which shows that he's just imagining everything.
• If you kill Big Horn during the attack in which he is holding Little Horn, Little Horn will spawn.
• In Greed Mode, there's a small chance that the Monstro will spawn before the Greed fight, which is hinted at in the trailer.
• When you defeat Rainmaker, it stops raining on the floor.
• The Notched Axe receives full charges when you pick up the Iron Bar, which is a play on how to repair tools in Minecraft.
• Faded Polaroid can open the strange door in Deep 2.
• Charm of the Vampire makes your reflection disappear in floors with water.
• tainted Lazarus reflection is always his other side.
• Lodestone ruins Dogmas Sprite.
• If you delete Blood Puppy's evil form with the eraser, it can no longer appear.
• If you have half a red heart and swap to keeper with Clicker, he will have half a coin heart.
• With Mama Mega and a golden bomb, you can use Mama Mega twice.
• The large bombs that only spawn in Ashpit can be turned into usable bombs using Safety Scissors.
• Mom's Bracelet allows you to pick up host heads and make them vulnerable.
• When small champion enemies die, they have a chance to drop a size-down pill. The reverse is also true for large champion enemies.
• If you enter a room with half a heart, Isaac pees on the floor, but with Eve it's blood, which is an allusion to the fact that God gave her her period because she ate the apple.
• Jacob's Ladder and other electrical attacks have more range in downpour and dross.
• When you defeat Dogma for the first time, but not The Beast, the image on the save file becomes a giant cross.
• If you use Esau Jr. more than five times in the same run, the glass breaks and spawns a red Abel.
• If you have both Berzerk and Suplex using School Bag, and Berzerk goes out during Suplex, a Mama Mega explosion will occur when you hit the ground.
• If you use Meat Cleaver in the Horny Boys boss fight, Hornfel (in his outside-the-minecart phase) and Loki will spawn.
• If you blow up the mirror in Downpour or Dross 2, you get minus seven luck.
• You can get rid of Tick with Match Stick.
• The Dogma item has an animated sprite, but you never get to see it.
• If you use the shovel in the tomb room in the Drak Room after unlocking the Forgotten, a chest will spawn.
• Great Gideon can be instantly killed with Chaos Card, which creates a crawl space beneath him.

Feel free to comment the facts I forgot, these are just a few that immediately came to mind.

They've lost contact with relatives because they believe they've fallen in with dangerous circles. Then they have to adopt a child because their relatives were blown up, which must have reinforced their theories. To protect the child, they try to raise them away from such things and "cure them of the magic." Then some letters arrive from a magic school, and at some point, they even move house to Tangier because of it. Then a giant comes to the house, makes your son grow a pig's tail, and takes the child away. After some time, the child returns home and says they'll be attending this school and will only be back for the summer holidays (imagine the effort involved in pretending the child attends any normal school). Over the summer holidays, the child returns and bewitches both their nephew and other relatives, and makes a cake float in the air. Then the child tells you they're friends with a murderer and traumatizes your child so badly that they're severely scarred. A few years later, they see a man covered in scars at the train station, and a few years after that, they're simply evacuated from their house because some sorcerer supposedly wants to take the child they've looked after for 17 years. And those are just a few of the things that happen.