Brian,
Substantially different. .NET is very structured, similar to "C++" (the result of their CRL). You will at least have to declare all variables, the days of variant are gone with .NET. Some of the things like control arrays are also gone. Note: .NET 2002 is different from .NET 2003. If you're going to update, go with 2003.
The real benefit of .NET is that it's a lot easier to create web based applications(nearly impossible with VB6).
Kevin