My closest express bus line also runs during peak hours only. I've never taken it because, from the MTA's timetables, it would be slower (due to traffic) than taking the subway.

However, overnight, I take a 24/7 express bus from Manhattan to S.I. and then transfer to the SIR to finish my trip. Overnight, the express bus makes it from FiDi to Old Town in 20 minutes flat. Shaves a ton of time off of waiting for the S.I. Ferry (which often goes to 1-hour headways overnight) or, worse, crawling down the Fourth Avenue line in Brooklyn on the R (which is godawful overnight).

I don't know which part of the city you're in, but I'm pretty sure there are 24/7 express bus lines to every outer borough. Perhaps you might look into taking an express bus to a subway line convenient to where you live. Even though you'd still be taking the subway for the "last mile," that could still help you save a lot of time.