Do you think the discrepancy between the window layout config in isboxer and my screen size would be the problem?
If it happens with just launching a window via IS, it's got nothing at all to do with your ISBoxer config. I don't know what "discrepancy" you're describing though, if the screen size in ISBoxer isn't your current resolution/screen layout, you can create a new window layout that has the right sizes, or in the Computer box on the right hand side in the region editor panel, select Current Computer and it will update. Otherwise the sizes shouldn't matter one bit, anything you can configure through ISBoxer should be supported. That is, unless you have the window set to be a larger size than your desktop size, in which case I could fathom this being an issue.

But no, it'd have to be something to do either with other mouse software or window management software, as if somehow you're changing how the mouse or game window is working, or you somehow have a combination of options selected that nobody else has selected until you, that happens to produce this issue in combination with Inner Space.