You get a lot more points for longer letters; try to spot those five- and six-letter words before making shorter words. Making a lot of three-letter words will use up your cubes without giving you a lot of points.
Look for things that can lengthen your words: the letter S to form plurals; endings such as ER, ED, and ING; or prefixes such as RE and UN.
You'll use your cubes most efficiently if you use all its letters a few times before the cube gets removed, rather than just using one of its letters four times, while leaving its other two letters unused.
Try to avoid removing cubes that result in "holes" in the pile; these holes create dead spots that make it harder to form words.
If you are going to make a word of questionable legality, try to avoid "using up" a cube when making that word - because, if the word is thrown out during the post-game dictionary check, you'll lose the cube removal points as well as the word points.
Don't wantonly remove cubes manually - you might find yourself with all your cubes gone, but plenty of time left. On the other hand, don't be afraid to manually remove a cube if you're having trouble finding words.
If you are stuck, and decided to remove a cube manually, remove the cube with the least helpful letters (J, Z, V, etc.) or that will expose the most new letters.