Hi Nate - If we are not near our limits, we suspend after a certain amount of non-opened emails. We have deleted non-responders when we were close or over our database limit and used a time frame of I believe 120 days of no activity.
There are several threads related to this.
Inactive leads that aren't customers should be removed and backed up someplace else. Your criteria is up to you. I usually do 6 to 12 months or target bad emails first. Also look at the Stage with Sales because you don't want to delete leads in process.