I am still unsure why this happened.
I tried unplugging the XBOX WIRELESS USB adapter, and it seemed to fix the problem.
Plugged it back in without reconnecting the controller, and the game worked flawlessly.
Finnaly, I have connected the controller, and tested again. Trying to ALT+TAB back or click on Aquaria via taskbar, will bring the game back into focus...after about 10 seconds of lag. From that point, it works just fine.
Windowed-Mode is a bit more responsive in bringing the action into focus again.