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Soy Milk and Tiny Planet may be bad by default, but they have some frankly absurd synergies. Once saw Soy Milk in a run and was going to pass it up, but then realized "hey wait a minute, I already have Technology Zero and this will actually work better with that than the Polyphemus I picked up earlier because Tech Zero be damned it's Polyphemus." Then I got Jacob's Ladder so I could get half-decent roomwide DPS just by shooting a wall continuously, and eventually had to because I mistook Proptosis for Pop.
You could win the game with it even without Pyromaniac, but don't any of you tell me it's still as versatile as it used to be, it's only gotten harder to not kill yourself with it, which makes it an easier item to skip.
Don't even get me started on Epic Fetus... If Dr. Fetus is sitting in a bad spot, Epic Fetus is that times 10, or even 100. It's stronger, may even be a sure way win, but it's such a boring item.
I think in general most items could do with a bit of a buff, maybe even go as far as retiring some of the most egregious examples that no longer have any room or justification to exist in the game, because there's a lot of items right now, so many that the rarest items are even more rare now than they used to be during Rebirth's launch. I'm talking about especially egregious ones, like Lemon Mishap, Holy Water, or Shoop Da Whoop!.
With how many items there are right now, you could move every single WotL item into a different kind of challenge run, one that turns the game back to the old rules of WotL for the most part, as far as items, shops, enemies and floor layouts go, which houses all WotL items, you could call it something like a "Classic Isaac" mode.
edit: oh right, over-hated items.
Odd Mushroom. I know people don't like damage down, but I usually prefer the tears up it provides. Still, there may be some good arguments against it.
Self-Damage items. I know they're probably not that great to use, but I still try sometimes to find use for something like the Razor. Still, I wouldn't go too far defending most others like this.
I still try to use it every now and then though, so if you can manage it all, more power to you.
Over hated for me is definitely fire mind. I find it to be alot of fun and really good, but i see tons of fire mind hate
Of course, if you still don't like 'em for other reasons, that's fine! But overriding your previous synergies shouldn't really be an issue anymore.
As for the Brain, the issue is that it's an explosion tied to your basic attack and those remove close-quarters combat as an option if you don't have one of the two items that protect you from explosions (both of which are exclusive to the massive Treasure Room pool and one of which has the "Special" tag that makes it significantly harder to find). Add to that the fact that it only triggers on enemies and therefore can't be used to open Secret Rooms with any real consistency and you've got a significant drawback for an admittedly pretty strong damage-dealer.
Curse of the Tower: Yes, I get why people dont take this. But I personally find it useful. If I get hit, a giant revenge blast is likely to take out pretty much everything in the room, break lots of rocks (which could lead to free stuff), and as long as I pay attention to the bomb positions, I can avoid them when they fly all over. Enemies, however, arent very good at the dodging.
Butter Bean: Why? Because if you pick it up and drop it enough times, it becomes "Wait, What?" which can just endlessly smash the crap out of all the rocks.
Mom's Bra/Pad: I know, I know... freaking gross. But look, I care about results, and these work on those stupidly irritating rooms stuffed with enemies that use pure rushdown tactics. Those rooms drive me crazy, but these can counter that completely.
Missing No.: It's hilarious. That's really all it needs. But also it can be darned nice if I'm having one of THOSE runs. You know, the sort where I'm just getting nothing and have a really godawful build... may as well take my chances with this crazy thing.
Tiny Planet: Utterly devastating when used right. Situational, sure, but... yeah, I've had more than a few totally loopy runs with this thing.
Broken Modem: I've heard quite a few players complain about this... I dont get it. I always take this when it shows up. It just outright makes things easier to dodge.
As for overhyped items, the big one that comes to mind is Dead Cat. I hate it. I just hate it.
Also not particularly fond of the sorts of items that almost guarantee a win just by themselves... they're just dull. Fortunately there's not all that many of those.