Infestation 2. This item is such a sleeper powerhouse.
It spawns a blue spider on anything you kill at a 100% chance (that isn't killed by a blue spider or some sort of NPC-driven kill like Charm or spikes). People never appreciate the incredible power this item provides. While it obviously hinges on your ability to kill enemies, if you can get the train rolling, it snowballs into absurdity harder than any other item in the game. It's valuable for offensive, defensive, and utility. Nothing about it is bad.
Even better, blue flies from things like Guppy Form stack with it, as anything killed by the flies will spawn a spider! And if you can get Hive Mind with this? Man, screw anything else at this point, the run is finished.
Godhead. Most people are going to take offense at this claim, because it's a fantastic item. But I'll explain why I say it's the worst item in the game.
First off, it encourages you to use Angel Rooms. The Angel Room item pool is 100% inferior to the Devil Room pool and even worse, the Angel Room regularly spawns Eternal Hearts instead of items (with the only alternative being the D6/D100 and rolling the Key Piece 1/2). Red Hearts are worse than Soul/Black Hearts.
Why is the Angel Room pool inferior to the Devil Room? Because the only stat increases in the Angel Room are from The Halo, Sacred Heart, and Godhead. NOTHING ELSE gives you stats or valuable secondary effects except flight that are exclusive to the Angel Room item pool (The Soul, The Mind, The Wafer, Habit and Holy Mantle are all available elsewhere). Compare that to the Devil Room. Most of the items in the Devil Room, without saying they do so, upgrade your damage, the most valuable stat. Then you have things like Contract From Below that is an insane wealth multiplier and shenanigans-enhancer (Contract From Below with Guppy's Tail and 1-2 luck pills is amazing in The Chest). And if absolutely nothing else, the Devil Room can lead to Guppy Form, which is so damn powerful that the Angel Room nonsense may as well not exist because of it.
Secondly, as far as I can tell, it doesn't spawn. Ever. In 100+ Angel Room attempts (including one where I had Habit+Pyromaniac+Ipecac+D6 in Caves 1 and rerolled Eternal Breath+Key Piece 1 long enough that it started giving me Boss Room items), I have seen Godhead TWICE. It never fucking appears. I swear it's a fucking bug or something because it just doesn't exist in my game. I mean, Eternal Breath and Dead Sea Scroll are obviously worse items to see in the Angel Room but the key thing is that you wouldn't have encountered them most of the time if you weren't trying to get that damn Godhead.
Because of its insane rarity, the insanely bad items you take in exchange for the good Devil Room items, and the insane aggravation involved in unlocking it (seriously, playing HM Lost was like unlocking the crystal ship in FTL for levels of bullshit), I consider it the worst item in the game. It's a tease of an item that has ruined more than one run for me in my attempts to seek it out. The only good part about Godhead is that you unlocked The Soul and The Mind to get it.
Death's Touch.
This is one of those items that is never bad. It gives you a huge tear hit box, penetration which is probably the most valuable basic tear modification in the game, and a significant damage upgrade. And even if you have something like Brimstone, it's one of the larger damage upgrades you can get. Fuck, it's even in multiple item pools so it's not locked to the Devil Room. And as far as basic tear builds go, Death's Touch has zero drawbacks. It's such an incredibly good item and can turn almost any mediocre run into a great run.
Easy. Fire Mind, specifically Fire Mind with nothing to override the exploding bullshit. It's like Bob's Brain except worse because it's random and unpredictable. The only run I've had success with Fire Mind is one that started with Pyromaniac on the first floor.