With the change to the new Season 2 mastery trees, we suddenly have many more options to choose from. While the masteries in Season 1 were very "fixed", we now have multiple good choices in every tree.
More now than ever, we want to zero in on the key masteries. In Season 1, it was enough to pick two trees to dump 21 and 9 points in, but the new tree's flexibility mean we need to pay more attention. Don't feel that you have to put 21 points in a tree just to fill out that category - 19, 20, 22, or some other split is perfectly fine so long as you gain a real benefit.
Let's quickly go through each mastery tree and pick out the best and worst ones. I'll mark especially helpful ones with "+++" and generally worthless ones with "---". As always, take my advice with a grain of salt, and just remember that just because I don't mention a mastery doesn't mean it's not worth investing in.
+++Summoner's Wrath (improves Exhaust, Ignite, Surge, and Ghost)
The new "summoner's improvement" masteries are much more accessible now. If you're using the appropriate spells, you have now have no excuse not to improve them.+++Alacrity (+1/2/3/4% AtkSpd) -> Weapon Expertise (10% ArPen)
The attack speed is meh, but the armor penetration is fantastic considering how early it is in the tree. As some commenters pointed out last time, choosing this mastery makes ArPen runes less necessary.+++Sorcery (+1/2/3/4% CDR) -> Arcane Knowledge (10% magic penetration)
Pretty much a no-brainer. Both of these are quite valuable for most champions. "AD casters" (e.g. Garen, Riven) may be content with just Sorcery.+++Sunder (+2/4/6 ArPen)
Gives the same benefit as 3.6 ArPen marks or 2 ArPen quints.+++Archmage (+1.25/2.5/3.75/5% AP)
300 AP = 15 bonus AP, 500 AP = 25 bonus AP. If you're stacking AP, this is more helpful than Blast (+1 AP/lvl).+++Executioner (+6% damage on targets below 40% health)
Helpful, but you don't need to invest 20 point in offense just for this.---Demolitionist (+10 damage to towers)
It's just not that noticable. For comparison, non-nexus towers have 2550 HP.Defense (link)
+++Summoner's Resolve (Improves Revive, Heal, Cleanse, Smite, and Garrison)
Take it if you're using one of these spells. Revive ftw.+++Tough Skin (-1/2 damage from minions and monsters) -> Bladed Armor (return 6 magic damage from minion and monster attacks)
Bladed Armor will drastically quicken your jungling. Advanced junglers can use this mastery to finish off monsters instead of wasting an auto-attack.+++Initiator (+1/2/3% Move Speed when above 70% HP)
350 MS = 10.5 bonus MS, 400 MS = 12 bonus MS. Especially great if you have an MS steroid or are using Swiftness quints or masteries.+++Enlightenment (+0.15/0.3/0.45% CDR/lvl)
Investing all three points gets you 8.1% CDR at level 18. Tanks usually can't afford to buy CDR in the field, so this is a nice option.+++Juggernaut (+3% max HP and +10 Tenacity)
3000 HP = 90 bonus HP. Tenacity is a very important stat, so get this if you can! This mastery DOES stack (multiplicatively) with Tenacity from items and abilities. Juggernaut + Mercury's Treads = 41.5 Tenacity.---Siege Commander (reduces armor of nearby towers by 10)
Ugh.---Honor Guard (-0.5/1/1.5% damage taken)
1000 incoming damage = 15 damage reduced. You can do better.Utility (link)
+++Summoner's Insight (improves Teleport, Promote, Flash, Clarity, and Clairvoyance)
Why not?+++Expanded Mind (+4/8/12 MP/lvl) -> Meditation (+1/2/3 MPRegen)
These two masteries will significantly help your mana pool and are a good option for any leftover points from Offense and Defense. Rank 3 Expanded Mind gives +216 MP at level 18.+++Runic Affinity (+20% neutral buff duration)
Great for junglers and AP carries who like wearing blue buff.+++Greed (+0.5/1/1.5/2 gold per 10 sec.) -> Wealth (+20/40 starting gold)
For support characters, this is fantastic. An extra ward at the start of the game, plus 540 gold = 7 more wards over a 45-minute game!+++Strength of Spirit (+0.4/0.7/1% max MP is added to HPRegen)
The typical AP carry has 1000-1100 max MP at level 18 = +10 HPRegen. Even before items, that's a huge boost to sustain. I'd say go for it.---Scout (+5% ward vision range)
It's as if Riot didn't even test this one. 1100 base range = +55 bonus range - that's only a half-Teemo! It's not even perceptible. Maybe if it stacked with allies, or was +15%, or increased ward duration...---Sage (+40 XP on kills and assists)
It's the same XP reward as one minion. Not even one minion.
So that's it. Not a whole lot to it, really. Just be sure to decide ahead of time which masteries you want to use with your character. :)