I have just made a small little app of a Python wxPython script with py2app. Everything worked as advertised, but the app is pretty big in size. Is there any way to optimize py2app to make the app smaller in size?
py2app or any other such packager mostly bundles all dependencies and files together so that you could easily distribute them. The size is usually large as it bundles all dependencies , share libraries , packages along with your script file. In most cases, it will be difficult to reduce the size.
How ever, you can ensure the following so that there is lesser cruft in the bundled application.

Do not use --no-strip option, this will ensure that debug symbols are stripped.
Use "--optimize 2 or -O2" optimization option 
Use "--strip (-S)" option to strip debug and local symbols from output
Use "--debug-skip-macholib", it will not make it truly stand alone but will reduce the size
I am hoping that you have removed unnecessary files from wxPython like demo, doc etc.
Slim down Python wxPython OS X app built with py2app?