The answer is, of course, that different is simply different. Whether it's good or bad depends on your tolerance for change. I've spent years as a Groovy/Java developer. That experience makes Clojure's dialect seem quite exotic. If, on the other hand, I was a Lisp programmer from way back, Clojure would most likely seem intuitively obvious.
As an object-oriented programmer, when learning a new language I immediately look for ways to do familiar things like define classes and declare variables. Clojure is a functional language -- there are no POCOs (for lack of a better metaphor), but there are defstructs. Everything is a function. Immutability is the default.
This impedance mismatch between my world view and Clojure's is captured best in the "Where's my for loop?" section. The answer -- "Clojure's for is not a loop but a sequence comprehension" -- tells me that I'm not dealing with a language that will simply require me to put my parentheses in a slightly different order. I'm dealing with some serious metaphor shear.
That said, I think that Programming Clojure does a great job of introducing these concepts in a brisk, approachable way. Another reviewer complained of spending too much time in REPL (an interactive Clojure shell -- think BeanShell for Java, groovysh for Groovy, irb for Ruby, etc.). I found Stuart's REPL-centric approach to learning Clojure to be a huge plus -- it gave me a sandbox to explore the language, experiment with the syntax, and run the code as I read it. This isn't a book that I could simply skim -- I had the Kindle edition open, sitting next to my laptop with a REPL session running at all times. Stuart also talks about compiling and deploying Clojure in production, but as a learning tool, REPL's pedagogic value simply cannot be overstated.
The fact that Clojure runs on the JVM, and allows you to call into any Java class, gave me the best chance to see these two very different worlds running side by side. There is an entire chapter dedicated to Clojure/Java interaction. As Stuart says, "When you call Java [from Clojure], you enter the familiar, mutable world. This offers a comfortable haven for beginners learning functional programming and a pragmatic alternative to functional style when you need it." The examples involving the Collections API, JDBC, and even simple HTML output, were the most helpful to me. They demonstrated not just the syntactic differences between these two languages, but the semantic differences as well.
As you can probably guess from my 5 star rating of Programming Clojure, I think that "different" in this case is unquestionably good. Reading this book has stretched me in new directions. Each time you learn a new language, it makes you better programmer -- even in languages you already know. It forces you to reconsider your existing, tried-and-true approach to solving problems. Programming Clojure is a long-term investment in my knowledge portfolio.