1. Performance: One key difference between .NET and Node.js is their performance. .NET is a compiled language that runs on the server, providing fast and efficient execution. On the other hand, Node.js is a JavaScript runtime that runs on the server-side, executing code in an event-driven, non-blocking manner. While .NET can handle high loads and complex computations efficiently, Node.js is known for its scalability and ability to handle a large number of concurrent requests.

2. Language and Ecosystem: Another difference lies in the programming languages and ecosystems associated with .NET and Node.js. .NET primarily uses C# as its main language, which offers a strongly-typed and object-oriented approach. It has a comprehensive framework and a large set of libraries that provide a wide range of functionalities. In contrast, Node.js is based on JavaScript, a dynamically typed and prototypal language. It has a vast ecosystem of modules and packages available through npm, enabling developers to quickly and easily plug into existing libraries and frameworks.

3. Concurrency Model: The concurrency model also sets .NET and Node.js apart. In .NET, concurrency is achieved through multithreading, where multiple threads handle different requests simultaneously. It utilizes the operating system's thread pooling mechanism to achieve this. On the other hand, Node.js follows a single-threaded event loop architecture, where a single thread handles all the incoming requests in an event-driven manner. This approach allows Node.js to efficiently handle a large number of concurrent connections with low overhead.

4. Scalability: Scalability is another distinctive aspect of .NET and Node.js. In .NET, scaling applications usually involves vertical scaling, where additional server resources are added to handle increased loads. This can be achieved by upgrading hardware or adding more servers. In contrast, Node.js excels in horizontal scalability, allowing applications to be distributed across multiple servers, utilizing the benefits of parallel processing and load balancing. This makes it easier to scale Node.js applications by adding more servers as demand increases.

5. Tooling and Development Experience: The tools and development experience also differ between .NET and Node.js. .NET has a rich Integrated Development Environment (IDE) support, with options like Visual Studio, which provides extensive code debugging, profiling, and testing capabilities. It also has a mature set of development tools and frameworks that aid in building robust enterprise-level applications. Node.js, on the other hand, has a lightweight development environment, with tools like VS Code being popular among Node.js developers. It emphasizes simplicity and speed of development, allowing for quick prototyping and iteration.

6. Platform Dependence: The last major difference between .NET and Node.js is platform dependence. .NET applications are primarily designed to run on the Windows platform, although there are efforts to make it cross-platform through .NET Core. Node.js, on the other hand, is designed to be cross-platform by default, allowing developers to write code that can run on various operating systems such as Windows, macOS, and Linux. This platform independence of Node.js provides flexibility and allows for easier deployment on different environments.

In summary, .NET and Node.js differ in terms of performance, language and ecosystem, concurrency model, scalability, tooling and development experience, as well as platform dependence. Both have their own strengths and are suitable for different use cases and development scenarios.