I have two hard drives in my computer -- one for Windows and the other for data. Here's how I have it set up:
Everything pertaining to Windows is on the C: drive, just where Windows put it. Except for one thing: my official Windows Documents folder. I have mapped that one folder to a folder on my D: drive, let's say D:\Docs. Therefore, most programs default to D:\Docs when deciding where to save my data, that is, unless I have told them specifically to use another folder.
Remapping the Documents folder is easy: Open File Explorer, right-click on the Documents folder, and choose Properties. Click the Location tab. Put D:\Docs (or whatever) in the little window, and click Apply. It will ask you if you want to move your stuff to there; I suggest you tell it No. I find it better to move it manually rather than letting Windows move it, because in that way I can decide exactly what to move and which subfolders to put it in.
Remapping the official Windows Documents folder has worked very well for me, because the only Windows stuff it relocates is the actual Documents folder, nothing else.
Using this approach has the added advantage of putting everyone's documents in that same location, because all user accounts have their official Windows Documents folders pointed to D:\Docs. For me, that is the best way to do it. Especially since my Data drive is also my shared drive; all computers in my house can access that drive, and all of them save their documents, etc., to that same drive and location. This makes backups very simple and prevents multiple copies of documents from being scattered among the various computers.
If you relocate your entire Windows user profile to another hard drive, and that drive crashes, your Windows user profile will be trashed. In my opinion, it's better to keep all of the Windows stuff on the same drive, except for your documents, MP3s, JPGs, and other personal items, which should be stored elsewhere.