Best item in the game? Maybe, maybe by itself, but even ignoring bugs some items have the most ridiculous synergy. For instance, just today as Maggie I got:
A Pony (passive flight effect, spacebar charge attack – it has an invincibility bug too if you’re into that sort of thing)
Fetus in a Jar (turns your normal attack into free bombs)
Mr Mega (makes bombs, including those by Fetus in a Jar, bigger and stronger)
Bobby-bomb (makes bombs homing)
Ouija board (makes shots phase through objects like rocks, works with Fetus in a Jar bombs).
I massacred everything. By that I mean I think I beat Loki in about 3 hits. Minibosses only took two. I think Mom’s heart may have taken 6 or 7, but it was over in 20 seconds.
If you have Wrath of the Lamb, you may also get a combo like Book of Revelations + Habit + 9 volt. 9 volt shortens the book’s charge to 2 rooms, the Habit restores one room’s worth of charge whenever you get hit, and the Book of Revelations gives one soul heart (and makes Horseman encounters more likely). This makes you more invincible to attacks that do a half-heart of damage, and effectively halves damage done by one-heart damage attacks.
If you want to talk bugs, Guppy is probably one of the best in the game. It lowers your health to one heart, but gives you 9 lives. If you bomb yourself in a boss room after you beat a boss and kill yourself, it will let you fight the boss again and get another item, over and over until you only have one life left. This is even more potent with the D6 because you can reroll the boss items if you get something stupid.
Though you can get some funny synergies with Brimstone, I’ve seen people over at another forum post a picture of Brimstone combined with some mushroom effects and other things that made the laser take up half the screen, that was pretty impressive. Even so, Technology (NOT Technology 2) is probably better than Brimstone if you get the Ouija Board, because there’s no charge (without the Ouija board it lacks the ability to phase through obstacles, but still pierces enemies).
The Lucky Foot (Cain’s Starting item) can be a gamebreaker too, though less reliably of one. For one, it makes all bad pills into good ones (meaning Range Down-> Range Up). Your chance at winning the shell game in the Arcade also goes from 1/3->2/3. If you start an arcade round with Cain and about 20-25 coins, it’s not uncommon for you to end the round with a blood bag from the blood donation machine, 30+bombs and keys, Skathole (the poop on head item that charms flies), and a Dollar from the slot machine (as well as miscellaneous pills and other goodies). If you have Cain, always gamble it’s his true strength.
I think Xaiter’s ongoing Let’s Play at Something Awful is good. Even better is his livestream, Honk! I’m a Cat. For instance, witness extreme D6, Habit, and Guppy abuse and activating Cat Mode with Judas. It’s become something of a joke that the game was made for Xaiter, he has the most incredible luck with the drops in this game. He dies occasionally, but overall his luck is really hilariously good.
Yes, I know this thread is about 6 months old, but most of these people are still around so meh.