Strengths:
-Faster. Smoother. More cinematic. More freedom of what type of character you want to play. Rules are more consistant with one another, eliminating the “clunk” factor. Much less of that “wargamey/video-gamey feel.”
-Easy to port just about anything from any other D20 product into your setting. Want more sci-fi related feats? Grab some from Star Wars D20. Don't like the wealth system? Use the one from D&D. It's that easy.
-Preparation time has been reduced by more than half = More time playing the game instead of setting it up.
Weaknesses:
-New mechanics might initially seem intimidating to new players. (For example, HP and spells slots have been replaced with smoother M&M style save-mechanics. For players who have used HP for all their lives, this might seem like a radical change.)
-Although the game was designed as a “toolkit” system, this does mean that most of the work of putting a setting together then falls to the GM/players. Some might like that (I do.) Others won’t.
-The rulebook is a little confusing in some areas (especially to those not already familiar with M&M.) Fortunately, the True20 website helps a great deal in clearing things up.
-Combat can be far more grim and deadly at ANY level, especially if Conviction points are spent unwisely. In other words, that 10th level badass can still go down in one hit- Not likely, but possible. (Some may not like that. I love it.)
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Overall, if you’re looking for a solid toolkit system that can be used to run a wide variety of genres, but with minimal time spent pouring over rules, definitely look at True20.