I had plumbers over when I was out of town, they told my wife the cast iron house main needed to be replaced, I'm not sure where this is, I have two cleanouts next to each other, one is vertical and the one right next to it (almost touching) is on an angle. These are both in my basement.

The main refers to the largest sewer/waste pipe, usually coming down vertically and running horizontally along a basement and out through the wall or floor. It rusts from the inside out and often more so at cleanouts. Go down and tap around to see what you can see, call that plumber to find out exactly what they were suggesting, and call one more plumber for a second quote.

Show us a picture of your clean outs.
Call plumber and ask what he is talking about. You don't replace a main unless you have a problem. A problem like a broken pipe which is very rare.

Post back with information and pictures.