Without a doubt the best man speach is one of the major events on any wedding reception. It is usually delivered right before the toast. Not everybody is build to deliver speeches in front of large public so this experience can be extremely daunting. A good advice is to have a shot of whiskey before to lessen your inhibition a bit. Don't get drunk though. You don't want your speech to stick in peoples' memory for the wrong reasons.
Try to be nice in your toast or speech and affectionate particularly to the bride and groom. A joke or two is recommended but not too much and also beware not to sound offensive. Thank the groom for all those years of friendship and support. Try to tell an anecdote from the couples' past. Make it funny or heart-felt. You should really make up your mind before if you want to stick with funny or serious.
Try to sound genuine. Don't have everything crammed into your brain, improvise a little. Make comments about the ceremony or reception. You can make some entertaining observations about the food, mention how wonderful the wedding ceremony was. When you start talking about bride and grooms past sexual exploits try not to make this part inappropriate. Know your audience, remember that what might seem ridiculous to you and your friends might not exactly be funny for the couple's parents. If you are uncertain show the speech before giving it to a bride's dad or uncle and have them approve it. There's nothing better than getting a fresh perspective.