We just finished to deliver our first big .NET system with a 4-Layered Architecture and domain objects. The proof-of-concepts is done also for big systems.
Because we use a 4-Layered Architecture, the same business rules describe in the Task Layer (or Service Layer, as you wish) are applied to both the desktop and the web versions of the application.
NHibernate has also proven its value showing that it has enough performance for any kind of systems. I am anxious to start building other layered object-oriented systems like this.