Ah yes i have the same problem. I think it is related to the Foreground options in Innerspace's EQ2 configuration. But i also think that it is required to be that way for isxeq2 to work properly... Think it was pygar that mentioned something about EQ2 having to be "foreground" for it to accept the mouseclicks/keypresses sent to it by isxeq2...
Though, if you never activate full screen it wont have that always on top effect, if you just use ctrl alt f (i think, else it is ctrl shift f ) to play in simulated full screen, then it won't give you that problem.
I hope it makes sense... just woke up, and i'm sick... and i misplaced my glasses >.<
Good luck,
//Ronin