Transit in the NY Metropolitan can be an exhausting nightmare or it can be a fun adventure. Like most things in NY it all depends on your reaction to it. Through a series of trial & error below is a list of things to do to make your way about NY area transit more enjoyable or at least less unenjoyable ;-)
Even simple trips doing from one part of Manhattan to another can turn into an hour if you get lost or have to walk 20 long blocks. Manhattan is a deceptively large place and just because it looks like a short walk on the map doesn't mean it is. Take the subway as many connection to get as close to your destination as possible. Trust me, you will get plenty of exercise going up & down stairs and walking a few blocks from the subway.
Google Maps (web & mobile version) do an excellent job of providing directions & connections through NY transit but don't rely entirely on it because you will find yourself underground without a signal and if you cannot read a subway map then you will have to resort to begging complete strangers for help.
Streets in Manhattan are like a grid and they are very straight and consistent. Numbered streets are positioned North (higher numbers) to South (lower numbers) and avenues are positioned East (lower numbers) to West (higher numbers). You can use these numbers as a compass and easily figure out which subway to go on since most subway lines in Manhattan run North (Uptown/Bronx) to South (Downtown/Brooklyn).
It's tempting when going into the subway to be coming down the stairs and hear "Ding... Ding" and think: "That's my train". It may be the completely wrong train or the right line in the wrong direction because remember each line goes in two directions (unless you are at the end of the line). You will find yourself on a train on occasion after rushing onto the wrong one, always double check yourself and make sure you are on the right line and going the right direction. It's not a big deal to get off at the next stop and go the other direction.
Avoid the Bus
If you live right near a bus stop that drops you off within walking distance of your destination then you cannot complain too much. For everyone else the unpleasantness of the stop & go driving on top of the unreliability of the bus makes it a terrible way to travel not to mention the Manhattan Bus Terminal being a daunting place to learn the NYC bus system by. Stick to the subway for simplicity & affordability.
During rush hours avoid them empty seats
Choosing a seat with empty seats next to you just allow anyone to sit next to you and during rush hour the entire place it going to be packed and face it you don't want the smelly guy that takes up two seats sitting next to you. Men, if your choice in seating is between an attractive young lady or an unknown quantity (and the possibility of overweight & smelly sitting next to you) you know what you are going to pick. Ladies may choose to sit next to a young clean guy or choose the empty seat and stand the risk of sitting next to a bum rambling to himself or mole lady.
Choose the Train (heavy rail) for Long Distances
The train is blazing fast over long distances. I swear I don't have time to even do small amounts of work before arriving at destination. Train rides will cost about double the fair of the subway but if your time & comfort is more important than choose the train.
Sidenote: La Guardia Airport Sucks
La Guardia is an awful airport. Commuting to it is terrible because you cannot take a train or subway without having to transfer through a slow ass city bus. Also the terminals are disconnected which means if you get dropped off at the wrong one you cannot walk through corridors to get to your desired terminal. Choose JFK (my 1st pick) or Newark (in NJ). Sidenote's sidenote: also JetBlue rocks if you have a chance to fly them, they make flying pleasant again).
I have a terrible sense of direction and I've gotten lost plenty of times, went the wrong way on the wrong line and wound up in Brooklyn instead of uptown, just work smart not hard in the NY transit system and you will be finding your way around in no time.