Borrowing an extract from RolandiXor's answer, you can create several new files and append pieces out of the large.blend file.
Appending
This creates a full copy of the existing data, which you can modify without issue and include in the file you are editing. You do not need to keep both files together. You are also fully able to edit the appended data (such as an object, material, or scene) without affecting the original file from which you appended.
Appended objects have an orange outline when first appended (with the default theme), but once you deselect them, then select them again, they show as normal objects do.
When you enter the blend file, you will be shown several directories, these are the categories in which a general scene is grouped. I would suggest moving large models (located in Objects) into their own files (and adjusting any modifiers that might be on them such as subsurf) and if you need to recreate the scene again, use the other technique which is Linking which will allow you can attend to specific models without all the overhead of a cluttered scene.
It is a very good idea not to keep large scenes that consist of several models, multiple textures and effect systems in one file but to rather distribute these over several files and then link these into one file. The advantages of doing this are numerous.
To efficiently work with a heavy scene or dense meshes, you can find several tips here.