One of the more important fundamentals, easy to mention in just a few words, and can be used to springboard a few other LW thoughts - this is a pretty good candidate.
It's easy to mention in a few words, but I think that it deserves elaboration. I'd say the earlier comics suffered for spending too little time explaining and justifying the ideas in favor of including more of them. Better to learn and understand one idea in practice than simply be made aware of ten.
That a rationalist's strength is being more confused by fiction than by reality - if your theory can explain everything, it may as well explain nothing, etc.
You could do something slightly more technical about Bayes law (for example). Since these things are expressed better in written form than spoken, it might be worth taking advantage of that.
Hm... I'm not sure I could do reasonable justice to that, especially in a way that interests my target audience, without devoting the whole comic to that one issue. Though if anyone could suggest a way to compress Intuitive Explanation to fit in just a few panels or less, I'd love to hear it.
What if rather than a single comic on it, you did a short series centered around a Holmes-ian detective story that first shows how to identify evidence, and the sort qualitative aspects of plausible reasoning, and then showed that there is a general method for incorporating evidence in the final part?
A follow-up comic to Rationality Matters, describing the same general ideas but in a different format, is certainly a possibility.
I'm becoming more committed to producing a third Rationality Matters comic, and to make it the best as I can at what I want it to do: to persuade furries and libertarians to adopt LessWrong/Sequences ideas and become more rational.
I'm trying to use the idea from HP:MoR's chapter 25 about how to go about doing that... and, as part of that, I'm trying to figure out which particular LessWrong ideas to promote - things that are more specific than rah-rahing rationality as 'how to win'. Page-space is limited, and I doubt I'll make a fourth "Rationality Matters" in the same format, so... which LessWrong thoughts would you most like to see mentioned? Which ones do you feel are most valuable, or important, or at the very least are easy to compress into a comprehensible soundbite?