Yes, this is possible. Use a smart list and bring in the filter "Opened Email" and clear out the default filter of "Date of Activity". Then click "Add Constraint" and select "Min Number of Times". The selection for this constraint (ex. "2"), will populate the smart list with those who have opened the email at least twice.
Note that not all email "opens" are going to be logged as "opens" and there are false positives as well. More info: Email was clicked before it was delivered? It's a link scanner