I was lucky enough to have traveled through Istanbul this summer on my way to Syria and absolutely loved the city! It is truly one of the 'world's cities' that vibrates as soon as you step into its streets.
To add to our luck we were hosted by 2 excellent Couchsurfers, some of the most welcoming that we have ever stayed with. Both lived in distinct neighbourhoods (Beyoglu and Taksim, Orkatoy), which really gave us a sense of what Istanbul really is...an enormous net of neighbourhoods. My guidebook, Orhan Pamuk's Istanbul related this, but getting to see the city from these perspectives only made it more real.
If you want to get under its skin, start with the book mentioned above and then check out the Guardian's latest link to Istanbullus blogging about their city.
Looks like the city that bridges two continents is going to be the next "in" spot, but no worries, the city is plenty big enough to get lost in the crowd, as long as you try.