Let’s just get into this.

1. Skills and their tiers
ME3 moves from ME2′s 4 tiered power choices to a 6 tiered power choice. Much like ME2, you will select one of two paths at tier 4 and will do the same thing at tiers 5 and 6. You are not restricted to one path at tier 4, but can select either option at tiers 5 and 6 like you did at 4. Like ME2, each tier costs it’s tier in upgrade points. In comparison, both ME2 and ME3 have less tiers than that of ME1, but they both added some customization options that were missing from ME1.

Much like others, I assume the growth in tiers also means a higher max level than ME2, perhaps even on par with ME1.

2. Skills in ME3 are a fresh start
What I mean by this is that if you had the group Warp Ammo skill in ME2 and think you’ll go into ME3 with it, you’re mistaken. Same with any other skills you learned in ME2.

3. Ammo skills can still be trained for group affect
Each ammo skill has this option, typically at tier 4 like ME2. But, in ME3, the effect only imparts a 50% increase to the other group members and 100% to the character with the skill.

3. Grenades are different
In ME1, you could use grenades in a variety of ways which went missing from ME2, replaced by heavy weapons. In ME3 they return but the special function of them vary based on your class. For example, the Sentinel has a lift grenade (thanks SageHonor), which is an AE lift effect, the soldier gets a fragmentation grenade, and so on. Each grenade skill has its own 6 tiers of skills, including options to increase how many you can carry at once.

4. You are slower
Not sure why, perhaps to put more emphasis on combat gameplay from a tactical standpoint (more reliance on flanking and power use over movement in front of your opponents and to make melee a bit harder to get to). But, you can roll in a direction to go from one cover to another and close in on an opponent you may want to melee. You can still sprint, which seems to be about the same as ME2.