You are not alone in struggling with this. It depends on what type of file (ePub, PDF) etc you are trying to upload and then what APP you are going to use to read it. If you go to the Calibre FAQ you can see that they mostly recommend Stanza.
http://calibre-ebook.com/user_manual...-iphone-itouch
There is a section there titled "how do I use app with my ipad/iphone/itouch?" that should answer your questions.
I was trying to load a PDF file onto an iPAD the other day to read with the Goodreader APP and it was just as complicated.
I really wish we could do that one click "send to device" button on Calibre but since it is Apple, I suppose they feel obligated to try and lock it down.