John Dies at the End felt very much like a book that was written in pieces without a particular goal in mind, with weird episodic sections that didn't always tie together too neatly.  This Book is Full of Spiders: Seriously Dude, Don't Touch It comes together much more tightly, with a plot that's (mostly) coherent and character motivations that make a little more sense.

After the events of the previous novel, things haven't really settled down much in the town of "Undisclosed".  It's still a terrible town, with nothing much to recommend it.  David and John still are useless layabouts.  Only now, and infestation of weird spider-like parasites are taking over and zombifying people.  With humans mutating into super-killers and a government unable to quell the fears of the nation, the infected are quarantined in the hospital where they think the outbreak began.  Obviously David and John know better.

This book is slightly less insane than the first, but what it loses in crazy it picks up with a better story, even if it feels like a messed up comedy version of the Walking Dead.  There are still the swears and the reference to drug use as in the first, but it feels tamer, more accessible.  You certainly need to have read the first book to understand why John and David are special, and why David's dog Molly seems unusually clever.