So, before I offer any advice on how best to design a large schema, I need to ask one question: Is a large schema absolutely necessary?
You asked if there are any good software methodologies for planning large systems. Indeed there are, and one of the best approaches to complex software development is SOA: Service Oriented Architecture. If you wish to educate yourself a bit on SOA best practices beyond the database level, I highly recommend looking into Thomas Erls books, notably his SOA: Principles of Service Design. I also highly recommend listening to some of Udi Dahan's lectures on service-oriented and domain-driven design and architectures. Lot of good knowledge to be had from both of these guys.
When it comes to databases, before you dive in and develop a very large, complex schema, make sure you really, really truly need it. In a service-oriented environment, the motivation is to identify distinct, unbreakable boundaries between the distinct services of the business problems you are trying to solve. Once you have identified these boundaries, you should find that there are smaller schemas that can be created within them. Sometimes this leads to data duplication, as information must be published from one service to another when it needs to cross boundaries. But the benefits of having several smaller, less complex schemas can be huge. You gain greater autonomy, portability, flexability, and maintainability than you have with a single monstrous schema.
Look into SOA, particularly how to handle databases in a service-oriented architecture. The following presentation given by Udi Dahan should also provide some very useful insight:
http://www.vimeo.com/5022174