I am not sure about pod casts but generally if you delete a file in an MC Play list or from the Library that is in a sync list for the device it will be removed if you check the box on the device to "Delete files not in sync list" under options. As for MC know if you listened to it and then deleting it is beyond my expertise.
As for MTP vs MSC I have a Sansa Clip and use MSC. It has been a while since I made that decision but I never drag and drop files I let MC completely handle the Sync so no need for MTP. I have had my clip a since they first came out and I sort of remember having some problem with MTP but do not remember what it was but something to do with files stored using MTP where not seen under MSC and vise versa so I ended up with duplicates and running out of memory.