The game definitely feels faster and there are certain enemies you really gotta watch out for. (The skeletons and their thrown bones get me constantly.)
That said, I feel like the game is actually easier than BoI. Maybe that's because I played so much with "Everything is harder now" that downgrading is giving me a false sense of ease. But, for example, the Knights? In BoI with EIHN, would turn around at the drop of a hat to face your direction when you came up behind them. In Rebirth, they don't turn around for shit, and just let you shoot them in the back of the head.
Also I found a double locked room (takes two keys to enter) with the big die on the floor....no idea what happened, but
something happened, and I instantly got like 5 items added to my stuff. A familiar, a couple tear upgrades, the big horns.....not sure what happened there, because I think it actually removed several of my upgrades when it did that, but did not take them off my sheet.
I'm a little disappointed how easily the visuals get overwritten on Isaac. I was hoping in Rebirth that the visual effects would stack better, but they don't seem to. If you have like Mom's Wig and then get Leo, one will overwrite the other. Actual item abilities getting overwritten seems a little better, but it still happens. (Got Anti-Gravity Tears overwritten by the Cursed Tears.)
A couple things I've found too:
-Blue bonfires drop soul hearts about 50% of the time, and require bombs to destroy. There's purple bonfires too. I assume they drop Sin.
-The "Skull rocks" regularly drop Tarot Cards when destroyed.
-Mushrooms sometimes drop pills, mushroom collectibles or the Liberty Cap.
-While this true in BOI, the sheer amount of rocks in each level means if you get something like "Leo" and go destroy them all, a ton of shit will drop from them. Hearts, bombs, coins and other things. There's collectibles for rocks and poop that I've found so far that turn those rooms into Gold Mines.
-Secret rooms are no longer guaranteed to be found where they can connect to the highest number of rooms. The reason is that, for a room to connect to a secret room, I think you have to be able to walk the edge of the room. So all those rooms with pits lining the edges are not viable rooms to connect to a secret room. I've found the majority of "regular secret rooms" attached to the larger rooms. So, by process of elimination, it's sometimes easier to figure out where a secret room is, by excluding possible rooms because pits make them inaccessible.
-The Devil/Angel rooms are still pretty reliably found at the end of corridors, want 1 connection, and seem to like to show up near as possible to the boss room.
Only gotten a few Mom's Heart kills (and one Isaac kill) so far. Missile defense is way more important than it used to be in the original, because more bosses do bullet-hell style stuff now. And while Mom's foot stomp is smaller, it's actually way faster than in the previous game. Trying to fight Mom with Curse of Darkness is a big pain in the ass.