Running Routes: Is this route safe?

 It's certainly safe from a crime perspective if that's what you mean. At 5AM you might see a little traffic on 34th but not much. Okay, so traffic is relative! There's certainly less at 5AM than other times. Just be sensible and watch out for yourself.

 Note that you'll be running _under_ FDR, not on it! When you get to the waterfront you'll see a bunch of chain link fences and stuff when you first get under the FDR, but find the running/walking/biking path keep going as you have planned and you'll soon be on a nice promenade along the East River.

There's a nice path on the West Side too - if you wanted to you could cut across on Chambers street, go up the Harlem River, and then back to your hotel along 34th St. This run shows how to get across on Chambers if you want to consider it (but no need to cut across the Manhattan and Brooklyn bridges!):  http://www.mapmyrun.com/run/united-states/ny/new-york/999018597

 Also, running in Central Park is fantastic.

 Hope you enjoy the city! Almost anywhere in Manhattan is safe AFA crime (esp. below 110th st), and you just have to watch out for traffic if you're running on the streets.