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I've actually skipped boss relics before though. It depends on how much you value your gold gain.
As for Ectoplasm, I'd rather take that than dome, but ideally at the end of Act 2 or as a starter.
In general though, I would lean towards the Key (curses). You can choose to not open relic chests and thus not have curses (there are different chest designs which have different chances of good relics, so you can use that for risk assessment), just tank the curses (some of them aren't that bad), or just remove the curses (with the gold you can still gain from not taking Ectoplasm).
On the other hand:
If my run is strong, key lowers its ceiling. Also, matrioshka and juzu.
If I have anchor or my run is strong, dome is kinda win-more.
If I already have old coin or used maw bank, ectoplasm gets better.
Whenever I take curses I tend to get Normality, Regret, or Pain, so I've been traumatized into avoiding as many curses as possible lol.
Cursed Key translates to one extra curse and one to three fewer relics.
Ectoplasm translates to roughly 3 less card removes and loss of shop opportunities
Dome translates to a tremendous increase in difficulty for several significant fights - only take this if your deck is already winning. And yes, I have perfect knowledge of enemy patterns.
Key and Ectoplasm both have negatives that takes a long while to actually have any detrimental effect while Dome kicks in full force right away.
Lol, that'll happen, sometimes. Of those three, though, it's normality I fear the most (and the game seems to KNOW this, given the Mind Bloom event), and prioritize for removal. But as for the other 2, you eventually learn to use health as a resource and budget it, even on A20.
There's a good point here. Ectoplasm and Dome start having a negative effect on your run the moment you take them, and that continues right up until the final act.
Normality IS the worst one, yes. Unless I'm doing a Snecko eye thing, it chokes me damn near every run. But Pain is second worst because I don't like playing 1 or 2 cards a turn. I'm playing 4 or 5 generally speaking, and taking 4 or 5 damage every third turn is a lot over the course of an act.
Then try to have a deck that's thicker than 15 cards. Imho, that's arguably in the worst range of cards for a deck to have, until you reach, like, 55+. From 2 to 10-ish, or 20+, are far better.
It means you draw like 2 curses on average if you still want to get the chest relics. Honestly not the worst trade for 1 relic.