As stated Im using the latest Devel version of Inkscape.

1. Is there a way to change the default settings for the powerstroke path effect permanently?

2. Im experiencing some issues with layers. I cannot get a Blend Mode to stay set.
ex. I have layers 1 and 2 in my drawing.
layer 1 is set to Normal.
If I choose to set layer 2 to Multiply and then select layer 1 again, when I return to layer 2, the blend mode has been reset to Normal.
Anyone else seeing this?

1 - What do you mean by "default settings for the powerstroke"? If you mean the settings in the dialog, I haven't seen or heard of any way to do that. I guess you'd have to go into the code.

2 - I don't see that behavior in the stable version. But that's why I use the stable version! When you choose to use a development version, you have to be prepared for more bugs, or other "issues". You could always search Launchpad (bug tracker) to find out if this problem has been reported.

Edit
https://launchpad.net/inkscape