You can start by thinking about this novel's historic context and the audience that Lewis was addressing. This was a novel concerning the French Revolution, written for an English readership that was horrified by the events taking place and concerned for the loss of institutional authority (church, government, law). One question that could allow you to explore this idea is:
How does Lewis portray the danger of irrational, uncontrolled desires?
This question would allow you to touch upon both the individual characters (the criminal activity of Ambrosio and Matilda) and the larger historic framework (the violence and destruction caused by the angry mobs of the French Revolution). You could even delve into how these themes relate to the Gothic novel and its portrayal of supernatural events that mirror the horrific aspects of human nature.
Another question might concern Ambrosio's responsibility for his actions:
Is Ambrosio at fault for the crimes he commits?
You might bring up the fact that Ambrosio's repressed sexuality (he was a celibate monk) did not allow him an outlet for his desires and thus thwarted his potential to live a virtuous life. This question would allow you to balance an analysis of the environment that acts upon Ambrosio as well as his inner nature.