I haven't owned anything big in size but the smaller ones can't be layed down in the car or truck without leaking...or at least without potentially leaking.
I assume tho you mean big engine machines, and that being the case, about the only negative is the increased weight for the power output.
Otherwise they are every bit as good, and are similar to the issues you find with those in the snowmobile industry. Longer life expectancy, lack of oil being burned, and efficent on fuel use.
I haven't priced any of similar size, but if the price isn't any different, I would look hard at the 4 stroke. If there is a big price difference, then I would probably go with a 2 stroke as they are extremely well made and reliable.