I am far from a master of this game, but I've played it a shitload.
You may have figured some (or most) of this out after 20 hours, but heres a few things for Binding of Issac: Rebirth (I dont have the afterbirth expansion because it still isnt out on PS4). If you're new to the game, the health could be worth hanging on to. Deals with the devil are your friend but think hard before taking them, especially if you're just starting out. 
Both Maggie and Cain are easier for new players to play with, for the most part. Try to get a lot of money (without spending it) in one playthrough, and try to get a lot of hearts in one playthrough (without trading them to the devil).
Try to unlock the first two training wheel characters. So if you see a red/white pill and it's a health up, it will always be a health up in that game. Pill colors are random at the beginning of the playthrough but are consistent within one game. Always take pills! If it's bad, you'll only take it once but if it's good, you'll know what to look for. They can be a stat up or down (anything other than damage), as well as a couple of other miscellaneous effects. Pills: at the start of each game, you get a random set of 6 pills. Enjoy it! I have all the items memorized and it was fun getting there. The game will be a bewildering nightmare until you start figuring out what things will do. It allows you to make a bee line for the boss rather than explore, which is important. For the late game, The Compass is probably the most valuable defensive item there is. You'll get money, most often, which is very valuable. If you see a blank, black space on the map that is bordered by 3 sides, throw a bomb down. It's almost always bordered on three sides. If you have a bomb or two, it's worth looking for the secret room. When an item says it "appeared in the basement" that just means it will now spawn (some items you have to do particular things before they'll spawn) it doesn't necessarily mean that they're somewhere in your current game. There are some rocks that are suspiciously dark-grey. There's a pattern to where it spawns, though - it can only spawn in a 'blank' map tile with at least 3 rooms touching it (except occasionally on the first floor where there sometimes are no such groupings of rooms) A couple items will tell you where it is and you can find it by bombing walls. Always have at least one key to open that room. There's an item on every floor in a special room marked by a crown on the map and a yellow border around the door, but on every floor besides the first it's locked.
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