There's a constant worry about getting something nasty (malaria, rabies, dengue fever). The transport / roads often aren't very safe as they are usually in developing countries with very bad air quality in built up areas. In SE asia RTA are the biggest cause of deaths of western tourists. The bugs are annoying and you either have to use lots of pesticides / insecticides that aren't very good for you or something organic that is ineffective. You get hassled a lot and haggling is often essential and sometimes you just cant be bothered as it hot and humid.
Am I just getting old? I've done the whole a year in SE asia when I was younger and as much fun as it was, I don't partially want to go again.