Is it safe to be out late at night around 40th and Spruce right outside the UPenn campus?

Absolutely not

ttt

Question is, who are you more afraid of in that area, hardened criminals or drunk fraternity students?

ttt

I lived near that intersection for a year...and I would say yes, it's generally safe but some "street smarts" are required. I wouldn't recommend women walking by themselves too much after midnight. Most of the time that's a pretty busy interesection because there are 24-hour businesses on the corner. As long as school is in session, that is usually a pretty safe intersection/area