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Ever since Fallout 3 I've always turned off Auto-Save and almost exclusively use Quick Saves on my main character (still use manual saves on, what I assume at the time, to be an integral choice) and have had no issues so far.
"Nothing can stop the honey badger when its hungry." http://man-size.livejournal.com/523936.html
Both saves work just as well. I left my auto-save on default, and that means it auto saves everytime you change an area, which is pretty good if you change area/fast travel often. I tend to rely on quick save when traveling manually.
My auto saves recently stopped removing themselves from the load list after a period of time. Now there is just one slot available for a quicksave instead of the few I've been used to. When it got down to 1 slot, it would periodically decide to not replace the old quicksave with the new, in a particularly difficult area. I ended up having to play the area over many times, and still haven''t finished it.