Like with everything execution changes things dramatically, comparing a concept to something created from that concept doesn't make much sense. It is not good or bad.
Just making something huge and think it will be epic" is silly too (In most games it isn't because of how it is/are executed). ;D Anything can be realistic, even huge beings, if made with sense and logic. But from game mechanics point of view certain sizes of enemies will just not work well or not work at all, as Madoc said.
As an example of your first point. Look at Skyrim Vs Dragons Dogma.
Skyrim had huge ass dragons, but the mechanics behind them was poorly executed, hence the fights fell dull as hell.
Dragons Dogma had huge ass dragons as well, but the mechanics behind them were decently executed (could be much better) hence the fights were actually somewhat trilling, and being a few lvls to low, fighting a huge ass troll, could take you quite some time, and you would have to stay on ur toes for the whole time.
Now I understand that to big creatures wont work in a isometric game. But huge creatures can be a good thing to a game, and a well made huge boss will (for me) be more trilling than a well made human size boss.
Using Lupicus (x10 times a human Norn in size?) from Gw2; it's a great example of a huge boss made right (not perfect though) the boss room is huge, giving the boss plenty of room to move around, the camera zooms out much more (Could be used in an isometric game as well) and he's not just a 1pixel wide character with a huge texture, (No weird clipping or similar) and in the end, the fight feels much more epic, just due to his enormous size.
Now I'm not saying that all bosses in Sui Generis should be colossal, I actually prefer if there's only a few, and optimal (Hence they can be a little bit more difficult, since they are not required to finish the game) I'm just saying that there are means to support big creatures, even in a isometric game.