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Randomizing your items is a big risk already, and constantly having your items re-rolled is awful and can lead to horrible builds on late-game floors. It's one of the reasons people hate Tainted Eden.
I'd probably say some candidates for worst items are:
TMTRAINER (Way too inconsistent, way more likely to softlock or just kill your run if you're unlucky)
Obsessed Fan (Just Shade but worse)
Clicker (An item that gets progressively worse as you unlock more things. Also crashes the game easily)
Battery Pack
But if we wanna get technical.
C-Section is the worst. Does absolutely nothing, is required in the current build of the game for Dead God (not on consoles though), and is not in any Item Pools, so you have to find some other way to get it.
Dunno what the worst item is, but the most disappointing one is hands-down Mom's Razor.
Makes the current room virtually unplayable and changes your stats slightly. I guess if you have Rock Bottom it's abusable, but if you have Rock Bottom you've probably got the run in the bag anyway.
Picked up cursed eye as The Lost once, it can be good with certain characters, or with Black Candle.
Post-update correction. C-Section now actually has a function, spawns correctly, AND is REALLY good. Clicker also doesn't crash/softlock anymore (still kind of a bad item tbh)