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I'm at a boutique litigation firm on one of the coasts. My hours have been low for the last 6 months and I am probably going to be laid off soon because the situation is not improving. My firm is a regional leader in a niche practice area, and the pay is market for a 3rd year associate.

I've been invited to interview at a large (but often derided) firm where I would take a significant pay cut and work on far more routine cases. Is it better to accept this mediocre job than to risk having an unemployment gap on my resume?

way too many variables man..... do you think you'll land something good in unemployment e.g. are you a highly desirable candidate in your practice area?

Look for another job other than that one? You're making it seem like there are only two options here (unless there is)

My practice area is so niche that it's hard to lateral to another firm due to conflicts. I've already conflicted out of a number of firms that would've hired me based on fit and experience.

I haven't yet interviewed at the "mediocre" firm, so this all may be moot if they don't offer me a position. But I'm looking at about a 20k paycut if I end up going there.

I'm not sure that the other position you are referring to qualifies as "mediocre", but according to a WSJ article, whether you should take the job may depend on whether you're male or female:

http://blogs.wsj.com/economics/2016/05/ ... -time-job/