I was never a big VB6 developer, but I have used VB.NET quite a bit. REALbasic is a great substitute for creating desktop applications, but there are some things it cannot do, such as create DLLs or COM objects.
The REALbasic language is significantly more robust than VB6: it's fully object-oriented, has introspection/reflection and even has some dynamic capabilities. The IDE is a lot nicer than the VB6 IDE. But VB6 is 10 years old now and REALbasic is updated regularly, so it ought to be better.
There is a weakness in the 3rd party control market. You won't find anything as good as the grid controls available to VB6, for example. Reporting has been a weak area until recently. REALbasic itself now includes reporting capabilities and there are several 3rd party reporting tools available.
I've created quite a few professional business apps for Windows using REALbasic, but I do all my development on Mac OS X and use VMware Fusion and REALbasic's remote debugger to test and debug on Windows XP/Vista/7.