You are asking a pretty monumental question. I'll try to distill the answer down as best I can.
4e emphasizes playability, fun, balance, and ease of setup/use. In doing this, it sacrifices some of the realism and breadth of options found in 3e.
One method it achieves this emphasis is by giving all classes similar groups of powers. All classes get some at-will powers usable every round, some encounter powers used once per combat/encounter, and some daily powers usable once per adventuring day.
4e also assigns certain roles to classes. Some classes are Defenders, who usually stay in one spot and hold the front line against attacking opponents. Others are Strikers, who deal a lot of damage but are not intended for front line combat. Some are Leaders, who give advantages to other party members and heal them. And finally some are Controllers who manipulate the opponents and field of combat.
By assigning these roles, the game tends to define how combat will proceed, and therefore allows the DM to more easily challenge the party and come up with opponents who have their own roles.
The role assignments are not set in stone by the way. You can, for example, not have a leader if your players choose, as all classes have at least some minor ability to heal themselves. However, the rules tend to assume you will probably have all four roles covered.
Many of the 4e rules are aimed at combat, and a lot of people report that combat seems more fun in 4e. One big complaint about 4e is that there are fewer rules regarding non-combat encounters (there are some, just not as many).
That summarizes most of the bigger changes in my mind. There are hundreds of changes, but those are the largest ones. You may find reading some other published summaries more helpful than this thread.
Also, one last note. I strongly encourage you to play the game a couple of times before making a decision. Hundreds of people report that the game plays differently than it seems from reading it. Do not assume you can grok the whole thing from reading the rules.
