It starts with the declared goals of the language:
Regarding security, I simply don't get the point of in-language, capability-oriented security. Until we can secure an OS, which we can't at the moment, the only workable solution is sandboxing the whole OS. Whether the language is safe or not doesn't matter, if you can't trust the OS, and if you want to work with unsafe languages. Again, solve it out of band.
Reflectivity seems to have become another word for "things that shouldn't be done in the first place", like say, ActiveRecord's method names like find_by_name_and_email() or whatever. (This is simply a sign that you're lacking macros, which would allow you to do the right thing and define a frickin' embedded DSL.) Of course, you should be able to introspect every object, class, etc, but I'm taking that for granted.
Regarding interoperability, there's a choice quote by Bracha: "the real world, the nasty stuff that's out there". Now, that's the attitude that killed the Lisp machines, killed Smalltalk, and will continue to kill whatever project takes that stance. If your reaction to the real world is "egad, nasty stuff", do you think you'll ever "interoperate" with it well?
After the introduction, Bracha has to explain Newspeak's precedence and parsing rules for minutes, because otherwise, as he says, nobody would be able to understand the following code. Syntax other than S-expressions is simply irrational.
Then there's this business about everything being a virtual method call. Now, if there's one language that combines virtual method calls and functions correctly, it's CLOS (and thus, Factor). And CLOS shows exactly that virtual lookup is not fundamental. Basically, DEFMETHOD works like this:
(defmacro defmethod (name params &rest body)
(put-method ,(get-the-class-of-param (first params))
(lambda ,params ,@body))
(defun ,name (&rest args)
(call-method (first args) ,name args))))
So, the virtual lookup happens inside an ordinary function, the generic function. Function calling is the primitive onto which the virtual lookup mechanism is layered, not the other way around. That's the sane, rational way to combine the functional and generic object-oriented paradigms.
(OK, I like to do as little "virtuality"/polymorphism as possible, although I do find it indispensable. The thought of having virtual lookups all over the place, when all I want is to read a variable or call a function kinda freaks me out. So probably I'm not in the right target audience to begin with.)
Taken all of this together, I find Newspeak a fairly ill-principled language for my needs.