The original iPhone had an aluminum backing, with a small black band that ran horizontally along the bottom of the back of the phone. If you covered this area while using the phone, you'd find that your EDGE speed would drop dramatically, and you would lose signal strength. Once you knew this, you had the choice between avoiding this area with your hands for maximum network performance, or holding the phone exactly how you liked and having reduced performance.

The iPhone 4 (mine, at least) has the exact same issue, and it's almost in the exact same place, the only difference being the reasoning behind why it happens (in this case, it seems to be about bridging two pieces of metal with your hands), and how it can be avoided (buying a case might help with the iPhone 4, whereas it didn't with the iPhone 2G).

I've owned many other phones that were sensitive to where you held them, in fact I think every phone I've ever owned without an antenna that sticks out is sensitive to this problem to some degree. I had to "train" myself not to cup my hand behind the top-backing of the Nokia I had before my iPhone. And now I'm already "trained" from holding my iPhone that I don't touch the bottom left of the phone when I talk anyway.

It's not a big deal, just something to get used to (and it might turn out that a case will resolve it, which can't be said about many other phones with this issue). It is a legitimate "con" when determining whether to buy the phone, but it doesn't deserve all the ridiculous comments about how the phone is somehow flawed because of this.

(And just to give some more specific details of how this affects my phone: if I put pressure on the bottom-left corner of the phone with my hand where the seam is, the signal strength drops: by 1-2 bars if I hold it normally, or all the way to 1 bar if I give it a death grip. In either case, the calls don't seem to drop).