Wow, I haven't posted yet, even I have a clear opinion on the topic.
To chose the best fitting difficulty some considerations need to be made. On top of all it should show interresting non-trivial solutions to the problems, which change with difficulty. They make a run entertaining to watch.
More boss HP vs. less boss HP:
If there's ammo in the game, it may makes the run look more interresting, due to the need of collecting ammo along the way, which requires killing enemies or opening boxes making the sections before the boss more entertaining. It also may show clever usage of multiple weapons. So the prefered difficulty should be the hardest.
However if there's no ammo limit in the game ammo management is no longer needed and thus the problem falls away and with it the interresting part. In this case the difficulty is free to chose. Sometimes the hardest difficulty is the most entertaining one in this case, due to boss battles being entertaining, if the game has different ways to attack, or because of the nature of the game (example:
2529M).
Enemies deal more damage vs. enemies deal less damage:
When enemies deal more damage it means less damage boost/getting hit when bypassing can be made. But it also means that the TASer needs to do health management, which makes the run then more interresting. When at easy difficulty, the game may let's you rush througth the level and do as many damage boost as possible; Damage boosts alone aren't as interresting as damage boosts and health management together.
The easy difficulty can be used when there's always a way to bypass the enemies without getting hit, which isn't slower. Or no damage boosts exist in the game.
Enemies have more health vs. enemies have less health:
Let's say the TASer is in need to drop an item from an enemy, it would be possible to kill him with one attack on easy difficulty without slowing down. But since hard difficulty is used, the more attacks can't be made without slowing down, it requires the TASer to compensate the speed loss and thus make its execution more interresting.
If no enemies ever need to be killed througthout the run, it doesn't really matter which difficulty is chosen.
More enemies spawn vs. less enemies spawn
More enemies could mean more lag and lag reduction is hard, but this shouldn't be an excuse to use the easy difficulty if the frame-rate doesn't drop significally in the overall run. At hard difficulty clever tricks to reduce the lag, like killing enemies or camera manipulation, are needed making the overall run more interresting.
In case the frame-rate drops significally the whole run, it makes the run annoying to watch, therefore the easy difficulty need to be chosen.
I personally chose the hardest difficulty when ever possible, even if it doesn't change anything.