We decided to take a motorcycle to My Tho from Saigon. The trip took about 2 hours each way and was really a pain in the butt. The next day, I did not want to see a motorcycle (which is impossible in HCMC!). For US$20 we hired round-trip transportation, and our guides waited all day for us at My Tho.
One thing to keep in mind is that Vietnamese people expect young Euro/American guys are here for the girls. If they stop for a bite to eat or a drink it's probably because they know a local hooker and want to drop you off so they can pick up a cut of the earnings. Our halfway stop on the way to My Tho had this very thing happen... the girl also was the waitress at the restaurant. Did she really follow me to the outhouse...? I said no, but how many guys take her up on her offer? Does she wash her hands afterwards.... if so, how... I saw no running water or soap. Damn....
If you decide to take a motorcycle, bring sunglasses and a cloth or mask to cover your nose and mouth. It is also easy to get 1/2 of your body sunburned as you drive south all morning, so use sunscreen!
And bring a pillow to sit on so you can walk the next day.
The only way around My Tho is by boat. You can stop at any of the islands and see quite a bit. There are official government-run boat companies and private companies. I read the government companies are the only "legal" tour companies, but we hired a private boat and had not trouble.
There aren't many roads on the mekong river delta... roads are replaced by water and most people seem to use boats to move about.. small rowing boats in the inner canals, motorboats in the larger ones, and there's a high number of car ferries covering the larger distances, and some going as far as Cambodia.
In each city there is a harbour or boat terminal, where tourist boats leave from... so even if you come there on your own, you can organize your personal mekong delta trip.