Marty Wasznicky and Scott Zimmerman have published a great article on MSDN on some best practices while developing BizTalk application.
Please read the detailed article here http://msdn.microsoft.com/en-us/magazine/cc163423.aspx
Below are the main points of the article:
1. Always Use Multi-Part Message Types
2. Always Try to Design Orchestrations with Direct-Bound Ports
3. Always Use Separate Internal and External Schemas
4. Never Expose Your Internal Schemas Directly in WSDL
5. Always Optimize the BizTalk Registry for Web Services
6. Always Set the Assembly Key File with a Relative Path
7. Never Overlook Free Sample Code
8. Debug XSLT in Visual Studio
Benny Mathew 
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