Giant buckets, which would release an absolute torrent of tears that''d be difficult to dodge if you don't skedaddle away from it when you bomb it, but will also be more likely to drop tears up items from within.

giant skull, it has a chance to drop a double black heart or reverse tarot card (if none are unlocked it drops a regular card) and it also has a chance to spawn a champion host

Fonts could spawn in Cathedral and spray tears when broken.

big pot
either spawns a variety of coins, or several types of spiders

maybe giant rocks that take 3-5 bombs to destroy high chance of dropping small rock a few soul hearts/keys or maybe even terra!

the suggestion above me is mega cool (and should be genuinely considered)

-Giant TNT (whatever the exploding barrels are called) work like giga-bombs

-Giant Fouls Gold (Rocks with coins on the inside) Will give lots of money and/or money items but has a chance to spawn a greed boss

Giant Fireplace: Shoots multiple flaming tears upon destruction spreading from the center (like haemolacria). The flame tears should hurt enemies and Isaac. Maybe it could rarely drop fire mind?

Giant Spike Rocks: After destruction it leaves floor spikes underneath where it was.

Giant moving boxes in basement that scatter wooden shards that damage you when walking on them and drop cards or family related items, such as torn photo, dad's ring, etc...

Ultra greed's dead body in secret rooms or special shops, They could have a more open mouth and empty eyes with the coin fallen over besides it to signify the body's decay. They take more than 1 bomb to blow up with a chance of dropping tons of coins and money trinkets and/or keeper related items (keeper's head, steam sale, etc...)

A giant counterpart to buckets, but instead of being just bucket they're a well (Function the same as the bucket suggestion from ectobiologist)

Giant Polyps, which could be styled as blood clots or something. Drops red hearts when bombed, and after multiple bombs explodes into a torrent of hearts, bullets, and a giant puddle of red creep.

a giant tinted skull that is really rare but gives you 3-5 cards. 1 is always the fool.

Giant Tinted Rock, it takes 4 bombs to destroy, but drops 4x the tinted rock drops plus small rock maybe?

Big mine cart, can hold 2 enemies!

Since the giant poop is based Off and only found in the dross, how about a matching one for the Ashpit?
Imagine A GIANT pile of ash, like it looks like you would need flight to reach the top.
Maybe you ran across is to kinda shake the ash off of it, and you would get buried treasure, or a few of the bone orbitals from Book of the Dead.

Reposting in a proper place and adding a little.

All of the following loot is just a suggestion.

Giant pot (basement and variations) - filled with spiders and money, has a high chance for a quarter and small chance for Dollar or 3-Dollar bill

Giant "tinted" rock. Very high chance for Small Rock, very small chance for rock bottom, 1-3 keys, bombs and soul hearts, guaranteed crawlspace maybe?

Giant gold filled rock (mines/ashpit) - quite obvious loot with small chance for penny-related trinkets.

Giant bucket (dross/downpour) - filled with enemies, tears but also a lot of money

Giant clog (womb/corpse) - filled with blood - tears and creep alike - with a very high chance for blood clot and filled with hearts/rotten hearts and flies/spiders if in corpse

Giant skull (necro/mausoleum and variants) - filled with spiders (50/50 friendly or hostile) hearts, cards, high chance for skull item and either bone-related boss or a haunt inside

And lastly:

Giant keeper, secret room/membership card room only. 50/50 to summon Super Greed with 2 Greeds or one of Keeper related items