I have never been a big VB6 developer, but I used VB.NET quite a bit. REALbasic is a great replacement for creating desktop applications, but there are some things that it cannot do, such as creating DLLs or COM objects.
The REALbasic language is much more stable than VB6: it is fully object-oriented, has introspection / reflection, and even has some dynamic capabilities. The IDE is much nicer than the VB6 IDE. But VB6 is now 10 years old, and REALbasic is regularly updated, so it's better to be better.
There is weakness in the third-party control market. For example, you won't find anything as good as the grid controls available for VB6. Until recently, reporting was a weak area. REALbasic currently includes reporting capabilities, and there are several third-party reporting tools.
I have created quite a few professional business applications for Windows using REALbasic, but I do all my development on Mac OS X and use the VMware Fusion and REALbasic remote debugger for testing and debugging in Windows XP / Vista / 7.
Update . Since 2013, REALbasic is now called Xojo (the same language, though).
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