I recently invested some time in a similar error report that reached me through the play store error reports.
An overview of some possible causes.
Missing Library
Since my app is tested before release and the issue only occurs approx. once a week I'm pretty sure mine isn’t a library issue. You should think in this direction if a build on your system fails and installing the app using ADB results in error on launch.
Cleaning and building your project could help if this is a local issue and make sure you have the latest version of both SDK and IDE.
In these cases it’s one class of your app or a library used in your app that triggers the error. This is an important difference with the next point where the entry point (Activity with MAIN intent or your custom service/Application object) of your app is not found.
If so look into the following questions & answers I’ve selected. They all have an accepted answer.
unable to instantiate application - ClassNotFoundException
Android Activity ClassNotFoundException - tried everything
Android ClassNotFoundException
Main Activity or Application not found
Misconfiguration of AndroidManifest.xml
More like a beginners mistake was quoted here before in one of the answers talking about the android manifest file.
Important here is that this error would always block your app from loading. It should build though but crash on the first use.
I’ve edited that answer, this is the important part:
Do not use the android:name attribute! unless you've implemented a
custom Application object.
The application:name attribute has nothing to do with the name of your
app. This is the name of a specific class to load as your Application
instance. That's why you would get the ClassNotFoundException if that
class wouldn't exist.
For the name of the app use the android:label attribute on this same
application node instead.
Suppressed: java.io.IOException: unable to open DEX file
Now it’s getting interesting! This was part of the stack trace logged in my case through the playstore. So I can create a build and execute that on my device without errors (whereas all previous errors would prevent any run).
An important comment was made to the following SO question Android Application ClassNotFoundException, Unable to instantiate application
Looks like the system has trouble opening your application dex file java.io.IOException: unable to open DEX file, this is before any of your classes are loaded, so it doesn't have anything to do with how you define your application class in the Manifest. – user2046264 Feb 27 '14 at 2:25
The important part here is the suppressed IOException. This indicates that an IO operation failed. Examples of IO operations are network and storage calls.
Another error report that goes into that direction is listed at Android to Unable to instantiate Application java.lang.ClassNotFoundException: where the role of the external storage provided by an sdcard is mentioned.
Some other similar questions indicate that this can be a user error. "/mnt/asec/..." indicates that the app is running from the sdcard. If the sdcard is removed it could cause this error. 3rd party apps or rooted devices can probably move an app to the sdcard even if its not allowed by the manifest.
If you’re desperate read all the answers to that question since there are some other paths listed also. Think of full package specification, use of singletons and more.
The point here is that both network and storage are IO.
For my specific case I checked all the devices that reported this error and found that they all have external storage support. So a user could install the app and move it to external storage, have the SD card removed and get this error (just a theory, not tested).
For more info on the installLocation options see http://developer.android.com/guide/topics/data/install-location.html
I also considered the network. On top of the stack trace detail page at the play store reports you get an overview of the occurrences of the error over time.
It appeared to me that the error occurred more around the times an update was released. This could support the theory that the user gets an update of the app, downloads this update that somehow gets corrupted. The installation goes fine but the first execution of the app results in the error (again just a theory, not tested).
Other resources
Finally 2 non SO resources that might help you:
https://groups.google.com/forum/#!topic/android-developers/JC7_qqwBRjo
https://code.google.com/p/android/issues/detail?id=72121