Good questions.  I asked something similar before signing on to SS.  I was afraid of diluting sales or losing them to the 25cent downloads.  I was told, however, not to worry;  most buyers use one or the other ... seldom both. 
That, I'm sure, is subject to change.   

I wrote this earlier this year: http://microstockexperiment.blogspot.com/2010/01/shutterstock-versus-istock.html

but....

this year does not play as I was expected in my post: SS is ahead of IS....

I upload the same images to all sites.  The only thing that has changed over time is that iStock's higher acceptance requirements have meant that I tend to photograph in a way that is most likely to appeal to iStock.  I've found that has given me a higher acceptance rate with all the other sites too.

My experience of Shutterstock vs iStock is that I can get a lot of sales quickly after submission at Shutterstock, and then, over time, sales of a particular image will drop off.  Some will continue to sell, and occasionally there's an inexplicable flurry of sales on an older image, but most of the sales will come when the image has just become available.  Don't forget that not all images will sell at sub price on SS - they do have on-demand and extended licence sales too - which are always nice to get.

With iStock, I find that every image in my portfolio has a fairly equal chance of selling at any time, and of course, in general terms, each individual sale tends to make more for the artist than it will on Shutterstock.  Over the long-term... hard to say... everyone will have their own stats on that, and SS's commissions increase at certain levels.  It all depends on your volumes and regularity of output (and image popularity).  Of course you can submit huge numbers to SS very quickly if you have a big portfolio, but with iStock it takes a long time to build up your numbers due to their weekly limits.

Hope that helps.