I've thought about this for quite a while. I think it's good to keep your options open, and have a plan worked out ahead of time that you can fall back on if you ever need to, because after you've got a body to dispose of you probably won't be thinking clearly.
Redundancy is the word. Even if one method fails chances are the other won't. We also want the crime scene to be as clean as possible. If you make a bloody mess, you will leave evidence behind, simple as that. Once you open somebody up there's nothing you can do to get rid of everything that might be incriminating. Just as an example you could give someone some poison that won't cause them to vomit all over the place (I'm not going to make any recomendations on a family forum like this) and then when they're on the way down you could strangle them. Neither method is likely to leave a mess when you're done. If you just poison somebody they might figure it out and call for help. If you just strangle somebody they might fight back and get away, or start breathing again when you're not watching. But if you do both at the same time chances are they aren't going to get back up. It's improtant to dress well because a desperate person fighting for their life might fight back and leave mark, and we don't want that.
It's vitally important that you know where you're going to ditch the body afterwards. If you don't have a means of disposal now when you're thinking clearly, you're not going to pick a winner after the fact when you're panicking. I'm not going to offer any suggestions here, but for me all my years of wandering around in the woods might just pay off someday. There are places out there where somebody, or several somebodies, would never be found. Redundancy is also important here. There are a variety of methods one might employ. If you're burying a body you might try burying the body deep and covering with a layer of dirt and then put an animal on top and then more dirt, so that if the grave is exhumed it might be assumed to be an animal burial and left alone. A weak feint, but possibly effective. You might try cremation and then burial. If the location is far enough out of the way creamtion in-situ is probably best. Of course dental work that could lead to an identification that could tie the deceased back to you should be removed and disposed of properly. Imagination and improvisation are key.
On the way to the location that you've picked out it's important that no one be able to identify you. You could borrow someone else's vehicle, but that could still be traced back to you if there was an investigation. The easiest and cheapest way to ensure that no one can identify your vehicle on the way to disposal, is to cover every inch of it in mud. So much mud that you can't even tell what color the vehicle is. It's not illegal to drive a dirty car, and while the car is in this condition no one will be able to identify it. Afterwards you just hose it off and you're good to go.
Obviously the perfect murder is much more complicated than this, but perhaps these pointers will help someone out of a difficult spot.