Thats a good question.
Its always recommended to split big VDBs into multiple layers of VDBs instead of one big VDB.
It is also important to have a specific purpose for each layer of VDBs. There is a very good technical whitepaper with recommendations on how you can do that.
You can download it here
Please note that with the flexibility and modularity of multi layer design comes the dependency of top layer vdbs on imported vdbs. You need to carefully evaluate and pick what is good for your situation.
From the performance perspective there should be no big difference between one VDB or multi VDB solution.