The main problem with Binding of Isaac is pretty much the item balance.
Stupidly strong items like the Scared Heart, PrayerCard, Brimstone etc.
The decent passive items which you generally prefer over almost any "active" item unless they're the over-powered ones.
The pointless items, like the Poop, Bean etc
The crippling items like IPECAC, My Reflection, etc
Some of the items could be easily rebalanced as well. IPECAC only needs the "Chocolate Milk" mechanic so you can charge how far the projectile will fly. The Bean should recharge without the need to enter a new room (it's pretty decent if you can get close enough), the poop just needs to be removed, nothing is saving that.
As for the nature of the over-powered items you could take a page out of the aRPG genre and have item percentage influenced by the basement level. The "lesser items" having a much greater chance of dropping in the first few floors.
For example, The Prayer Card item has dropped in every single game I've played. In god rooms, curse rooms, beggers and shops. It's insane how common that item is. It's also fairly insane how good the item is.
Now couple all the things I've said about item balance with the new enemies added in the DLC. To be perfectly honest the vast majority of the enemies are just cheap. There was some rooms where I entered and due to the lay-out of the room and the amount of enemies with cheap moves I took damage as soon as I entered with no way of dodging it, not good mechanics. Combat with the new enemies feels like: "get wings or good luck trying, pal".
I love the game but at this point it's extremely item based which means the game is almost competely random. The game has become both extremely frustrating (with the wrong items) and laughably easy with the right ones.
Now if you compare it to the orginal Binding of Isaac release which still had it's problems, it was still much easier to go through the game with the crappier items.
And finally I sugguest to any new player who wants to play Binding of Isaac. DO NOT buy the DLC untill you have a few "true" wins under your belt and all the characters unlocked. I would shudder to think about starting The Binding of Isaac for the first time and meeting Widow.