The original Mass Effect certainly had it's advantages. It probably has the best sense of exploration and discovery, the other games have their moments but get a little bogged down in the fighting.
It could be because they appear throughout the games, but I tend to think the original crew were also the best (at least the non-humans) since you can build more of a friendship with them than pretty much anyone else (other crew members tend to be restricted to "romance" or "ignore" options). Garrus was particularly interesting in the first game since you could influence him towards Renegade or Paragon ways of thinking but, unfortunately, that didn't seem to have a major effect in future games (though it's kind of touched on).
The way the first game handles "non-combat skills" is probably better as well, since you have to invest skill points in them and there's less of a need to consistently follow one path in order to use persuasion. The skills in general were maybe not quite as well designed as in later entries but they tended to include a bit more flexibility.
I think my main complaint against the first game is that the combat was a bit too easy and didn't often feel tactical, interesting or challenging (at least beyond the early levels). It wasn't terrible but in subsequent playthroughs it could start to feel like something you just want to get past to get to the good bits (maybe even during the first playthrough for some). I find the combat in the second and third games can be enjoyable in itself, which makes it a bit easier to go back to the games.
Saying that, I played the first game four times, the second one three times and the third only once. Maybe that means something.
I'd expect the next game to probably have similar gameplay to the third game but I really hope they at least bring back the exploration and character strengths of the first game (a new Mako is a good sign for exploration, at least). It would be nice if they could also find a better way to handle persuasion and maybe throw in some alternative skill choices that could make subsequent playthroughs more interesting/different by opening up new options.
