I think a mileage run doesn't hurt the airline much. What does hurt is the significant portion of mileage runners who are also chronic complainers (to get compensation or otherwise) and who pounce on mistake fares for themselves and 10 family members at a time. That type of customer can't be good for an airline.

I doubt the airlines have a problem with people who do one or two mileage runs a year to supplement normal travel patterns.