Creation Kit can be run via Mod Organizer and that is how I'm using CK. If you intend to do anything that involves scripting, then you will have to do a bit more work to set it up. MO, as far as I am aware, essentially sets up a virtual file system for whatever program you launch via MO. However the Papyrus compiler is 1) a separate program that is launched by CK and not MO, and 2) an AnyCPU executable (can run as a 32-bit or 64-bit program depending on the operating system) that may run as a 64-bit process, which MO does not support. There are two solutions that I'm aware of for this dilemma.
1) http://wiki.step-project.com/Guide:Mod_Organizer#Creation_Kit_.28CK.29 to force the Papyrus compiler to run as a 32-bit process. It has been a while since I last tried it out, but I think this solution still requires you to keep all of the script sources in the actual \Skyrim\Data\Scripts\Source folder, which kind of defeats the purpose of running CK via MO, due to the compiler not using the virtual file system set up by MO.
or
2) Use Advanced Papyrus (link in my signature). It is a small program that acts as a wrapper for the Papyrus compiler that allows you to both run the compiler from a CK+MO combo without modifying the compiler executable (apart from renaming the file) and modify the parameters sent by CK to the compiler so that you can keep \Skyrim\Data free of any scripts. The readme includes instructions on how to install the wrapper and how to set up the INI file in general as well as for use with MO. You can even have the script sources in various subfolders (e.g. SKSE's files in one folder, SkyUI SDK's files in another folder, and the vanilla Skyrim files in a third folder).
I usually just make sure to have the compiler set up to look for my mod's source files in \Mod Organizer\overwrite\scripts\source and output the compiled scripts to \Mod Organizer\overwrite\scripts. Plugins created via CK+MO will automatically be placed in \Mod Organizer\overwrite so they will be separated from other mods you might have installed via MO as well as from the \Skyrim\Data folder.
You can also have multiple installs of Skyrim and switch between them by renaming the folders. For example set up a fresh install of Skyrim, copy the entire folder, and install CK. You should now have one copy of Skyrim that you can use for playing the game with a suite of mods and another copy of Skyrim with CK installed for developing and testing mods. All you need to do is rename the folders when you want to switch between them (the one that you want to use should be called Skyrim, the other one can be called anything e.g. Skyrim - Mod Dev or Skyrim - Playing while not being used). If you want to use the least amount of space, then you can have a single copy of the BSA files and have the two copies of Skyrim use the same set of BSA files by using symbolic links, which can be created via the command prompt or the Link Shell Extension program.