Just had this problem with an iPhone 4s that one of my junior employees repaired for a customer, customer came back with complaints of the call recipient having nasty echo feedback of their voice after having the charge port/bottom mic replaced. One other thing about this situation is that when the rear glass was removed the problem disappeared.
After opening it up and having a look I noticed that the rubber gasket that usually sits over the microphone was gone. I tore apart an iPhone 4 that i had spare to get the gasket out, fitted it to the faulty 4s and the problem was gone.
My theory is that the mic was making direct contact with the metal frame, as the ear speaker at the top made noise (of the other person speaking) it caused vibrations through the case (or possibly the rear glass) which in tern made it's way back to the bottom mic causing the feedback. These microphones are pretty sensitive so it needs to be insulated from the housing with that rubber. Hope this helps!
Other things that can cause the problem are: Cases that block the top/noise cancelling mic (located near the headphone jack port, it's a tiny hole) or a faulty noise cancelling/top mic which is part of the headphone jack/volume button flex on an iPhone 4s and part of the power button/proxy sensor flex on the iPhone 4.
Always transfer over rubber gaskets/components when replacing parts.