I'm grown up buying things online so I feel comfortable with making purchases on the "interwebs". But there are two aspects that come to mind when I think of the term "safe" as it relates to online jewelry & shopping online.
1. Safe - Personal information? I'd say if it's a reputable site yes, go with the big names, Tiffanys.com, BlueNile.com, Ice.com for diamonds... or go through a shopping comparison engine (as they have legitimate advertisers).
2. Safe - Satisfaction. Now this is a little more unclear to me. I recently purchased a ring for my fiance, it was a big purchase - so I went into the store a number of times. I trust BlueNile.com with my information & their prices are great... but for the large amount of money I spent I needed affirmation & visual confirmation this tangible jewelry I was about to break the bank on!
In general, I've found that even online jewelers have a high level of service that they maintain. If it's a pair of faux pearls or emeralds why not get them online? My fiance tries it on in the store & then buys online - she gets a great price!