Becca, yes the Tweak ePub feature is available right from the main Calibre window under the right-click context menu when you select a book. It's so handy to have.
I notice you have a PRS-350 also. If you ever have issues with a cover not showing up on the Sony reader (and it shows up fine everywhere else), it could be an xml file in the epub. Simply delete it and the cover shows up fine (though you'll have to do another epub-to-epub conversion in Calibre first after deleting it). The file will be called something like roadmap.xml or cover.xml. I always delete it now using Tweak ePub before I do any conversions.
Another file which plays havoc with the Sony reader is the xpgt file. It will set spacing and margins on the reader that you can't fix by simply tweaking the css file. Delete the xpgt file and problem solved.
I also routinely delete all embedded charis fonts in my epubs as I have the Boroda custom firmware installed on my reader which lets me use a set custom font.
So far I have not seen any detrimental effects to my epubs by deleting these files. And it appears many readers (Stanza, Calibre's own reader) routinely ignore xml and xpgt files anyway since the issues they cause on my Sony reader do not appear in those other places.
Oh, and to be safe, back up your epub before using the Tweak ePub feature for the first time.