Secret Invasion may be a sleeper for most impact, in that it makes you look back on so many stories (and other events) to see who was really who at the time.
Mutants started reappearing the moment Hope Summers crossed over into mainstream reality. Which was before the Superhuman Registration Act got repealed in Siege. Not to mention that Civil War featured in more comic tie-ins and crossovers than HoM did.
I am talking about the general, overall impact of each series. In-universe is debatable.
Lesse, for quality, there's Annihilation, dug Messiah CompleX and Second Coming as a start and then culmination of that big plot arc... probably just various space and X-events filling out my list. The main line ones tend not to interest me much, though I do enjoy the aftermaths.
Also, Fear Itself on the impact list? Hah. I'm hard pressed to think of anything it did that stuck even for a year or two. Temp-kill Thor *again*. And, uh, anything else?
Annihilation turned Nova into a major character, eliminated the Nova Corps, made Super-Skrull and Ronan more major characters, and basically reshaped the space end of Marvel. Granted, the space end of marvel is overall pretty minor, but still. Muuuch more impact than FI. I'd put it at... probably 6 on their list. And IG above FI, of course, bump that FI off entirely.
Heck, the following *recent* events had more impact than Fear itself: Messiah CompleX, Siege, Second Coming, Utopia, Dying Wish (the whole SpOck thing), Annihilation Conquest (made the Guardians of the Galaxy a thing).
Yea, IG should be off too. Put Messiah CompleX in it's place...
Well, Civil War divided most of the major heroes into two camps, outside of the X-men, and kept the divide for a long time. The split from New Avengers (that were effectively just 'the Avengers') to New Anti-Reg / Mighty Pro-Reg kicked the Avengers up to a whole new tier of sales and transformed them from a book into a franchise, and why nowadays there's 4 avengers books instead of 1 like there was pre-CW. It also introduced the new Thunderbolts, kicked off the Initiative, and that sort of thing.
House of M eliminated most of the minor mutants and changed the situation of the X-men a lot, but the major ones largely stayed power or rapidly got re-powered (I think Jubilee might be the most major depowered mutant). So, in terms of setting it changed a lot, but the story impact on the main characters was less changed by that single blow. It was still the same characters running a school and fending off various threats.
I'd say the series of X events that started with House of M has more change, but it's not until you get stuff like the move from Xavier's to San Fran as a result of Messiah CompleX (which killed Xavier and moved the team!), Cyclops becoming a political leader more than a team leader, etc., that things drastically shake up. That whole X-men megaplot arc really was quite solid.