If you have a lousy selection of letters, often it is better to just swap them out rather than try to battle on. Most of the time you will only be able to play 2 or 3 letter words so will not dramatically alter the letters in play from one turn to the next. If you swap out the tiles you can possibly get a far better set and be into the big points once again!
If you get a Q, make sure you save a you to go with it. However, you can play 2 and 3 letter solutions to this dilemma, such as QI and QAT. All the same, having a you will give you far more options strategically.
Attack is always the best form of defense, but you should keep an eye out for potentially strong positions that your opponent may be maneuvering towards.
If you cannot make use of a multiply tile with a really strong play, it is often worth blocking it with a weak word just so your opponent can't use it instead. Similarly, don't open up the tiles to your opponent. If you play a very long word down the board, it will often open up many multiply tiles which will end with you losing points in the long run.
The Double Word and Triple Word score tiles are great on their own. However, if you can combine them in one turn, or use one multiply tile on more than one word, you will be rewarded with an incredible score for just one turn.
If you can stack words so that you play multiple words in one turn, your score will be considerably increased. For example, if you play a 4 letter word and then a number of 2 letter words in the same turn, you will be showered with points.
This is the closest you can get to cheating at Words With Friends. 2 Letter words are vital for creating a good strategy and can be crucial to winning at Words With Friends.
You can find a list of 2 and 3 letter words acceptable in Scrabble at http://phrontistery.info/scrabble3.html though there are many such lists on the Internet. Use this list to give you the edge in word-battle!