So I've been doing this commute for a long time. I kind of go back and forth, sometimes taking the 33rd St line and walking, or the 33rd St line and whatever comes first (B,D,F,M) to get near 53rd, or the 33rd St and then change from 9th to W4th and have even more options (B,D,F,M,E) --- or just going to WTC to admire the gorgeous station environs and taking the E local. If you feel like exercise bring a manual folding kick scooter and skip the subway part.

I was glad I didn't go the WTC route on 9/11, but other than that it's really whatever strikes you in terms of mood or how the trains are running.