"First Among Sequels" is brilliant. I may as well mention that first.
It's a chaotic book. Other reviewers have said that the lack of a main 'villain' is disappointing, I think the opposite- Fforde juggles various plots at the same time and the result is a sort-of murder mystery where any one of several different characters, in different worlds, could be the key. Among the various plot threads are some ideas of pure genius- for example the time-travelling authority the ChronoGuard who have been happily travelling through time on the assumption that time travel would eventually be invented in order to allow them to do it, but who have now reached 23 minutes before the end of the universe only to find that time travel hasn't been invented after all so they're not sure what they're going to do about it. Fforde refers back to ideas from each of the first four books and brings new things in at the same time. These books are heading toward bursting point.
With the ongoing Thursday Next series I'd say that you should definitely start at the beginning ("The Eyre Affair"), partly because you might find "First Among Sequels" very confusing otherwise, but also because reading this book will spoil your reading of the previous books, as , unlike something like the Discworld series, you'll know who's survived and who hasn't.
The fact Fforde is now five books into the series allows him to become introspective, and weave his own books and fictional versions of his own fictional characters (fictional squared?) into the narrative. When I first read that I was worried that this book would be in danger of heading, um, up it's own bottom. Thankfully it manages to avoid that and Fforde weaves "First Among Sequels" into the original "The Eyre Affair" in a way that enriches things rather than messing them up. I was reminded of "Back To The Future II", which in my eyes is a good thing.