I have two monitors running 5 WoW instances. Main monitor is 1920x1080, other is 2048x1152. I chose this layout "Multi-monitor on \\.\DISPLAY1 and \\.\DISPLAY2 (Swapping,Maintain Aspect,Avoid Taskbar)". It sets the mainwindow to 1920x1040. I have set the other instances to use the same resolution manually so I don't know what the layout sets those to. The problem I have is, because the resolution is 1920x1040 parts of the game UI is outside my monitor. If I use 1920x1080 everything is where it should be and I normally use this resolution, but ISBoxer wants to change it every time I load the game. I changed it to 1920x1080 manually on every WoW instance and get the popup in ISBoxer when I load. Does this mean I have to press "No" every time the game asks to change it?
No, the idea is to set up your Window Layout so that you don't have to adjust settings in the game manually

Your Window Layout is going to synchronize all of the in-game resolutions to 1920x1040. If you want all of them to be 1920x1080, then the easiest fix for you is actually to just set the Region size to 1920x1080 (thereby cancelling out "Avoid Taskbar"). Then when you Export, it will set all of them to 1920x1080 instead of 1920x1040, and you will NOT need to press "No".
If you want to KEEP "Avoid Taskbar", AND these window sizes, BUT sync them all to 1920x1080 anyway, then you will need to create an additional Region in your Window Layout for ISBoxer to sync the resolutions to. In the Regions editor, right click Region 1 and select Duplicate Region. It will make a Region 6 automatically. Resize Region 6 to be the full size of screen 1 (1920x1080). Then in the Swap Groups tab, change the Reset Region option to Region 6 instead of Region 1. Then Export to Inner Space. Now instead of syncing the resolution to Region 1, the resolutions will be set by Region 6. When using this method, even your main screen will be scaled down -- and note that because 1920x1080 is a different aspect ratio than 1920x1040 (just stripping pixels vertically..) it's not going to look right.
edit: Another thing with switching windows. Whenever i switch my main window to any of the others some of my binds gets executed; F11 and few others probably. Also I get spammed by "No player named 'CharacterX' is currently playing." I'm guessing it is something with the Jamba addon, but I didn't have that before I started using ISBoxer.
The Quick Setup Wizard generates some WoW Macros, including a Follow macro that gets bound to F11. You will want to change the Key Combination assigned to the "/follow {FTL}" WoW Macro. To change this, go in the top left pane under Game Helpers and select World of Warcraft. Then in the bottom left pane under the "Quick Setup 38" WoW Macro Set, select "/follow {FTL}". The Key Combination is set to F11, just change it to something else -- but it is important to note here that the key you set this special macro to (because it also wants to reserve all modifier keys) you will need to set it to a key without modifiers. (And that has no key bindings on Shift+___, Alt+___ Ctrl+___, Shift+Alt___, Ctrl+Alt+___ etc)
Note that after changing WoW Macros through ISBoxer (including changing what they get bound to), you will need to "/console reloadui" in the game, or re-launch (at least camp out to char select to reload)