I think it's a matter of : Which would make YOU happy?
Personally, if I'm even considering a designer item, I would prefer the designer. If I'm looking at a particular piece, it's most likely because I'm searching for a certain value/quality in that piece.
Some things I shop for don't need labels (like tee shirts, casual shoes and everyday items) and then others (like handbags, jeans/bras and pieces of jewelry that will be worn everyday and with me for a long time) I choose quality pieces, even if they're more expensive. It may be the prestige of the label, or even the personal preference for that designer, but I always FEEL better when I know that I have something of quality.
So ask yourself: Will you be happiest with the designer label? Or would you be OK with Blue Nile and not end up purchasing the Tiffany pair of earrings later? Because if you'll be purchasing a second pair, you may as well skip the BN and go right for Tiffany quality. But if you don't care and would prefer to save the money for something else, then Blue Nile will suit your purpose and very few people will know the difference.