Is my general line of reasoning correct here, and is the style of reasoning a good style in the general case? I am aware that Eliezer raises points against "small probability multiplied by high impact" reasoning, but the fact is that a rational agent has to have a belief about the probability of any event, and inaction is itself a form of action that could be costly due to missing out on everything; privileging inaction is a good heuristic but only a moderately strong one.

Sometimes, especially in markets and other adversarial situations, inaction is secretly a way to avoid adverse selection.

Even if you're a well-calibrated agent--so that if you randomly pick 20 events with a 5% subjective probability, one of them will happen--the set "all events where someone else is willing to trade on odds more favorable than 5%" is not a random selection of events.

Whether the Bitcoin markets are efficient enough to worry about this is an open question, but it should at least be a signal for you to make your case more robust than pulling a 5% number out of thin air, before you invest. I think the Reddit commenters were reasonable (a sentence I did not expect to type) for pointing this out, albeit uncharitably.

Is "take the inverse of the size of the best-fitting reference class" a decent way of getting a first-order approximation? If not, why not? If yes, what are some heuristics for optimizing it?

In my experience, this simply shifts the debate to which reference class is the best-fitting one, aka reference-class tennis. For instance, a bitcoin detractor could argue that the reference class should also include Beanie Babies, Dutch tulips, and other similar stores of value.