Well, there are a lot of games out there that are technically squeals but you can play them without any knowledge of the others such as, Final Fantasy, Resident Evil, Ratchet and Clank, Fallout, Doom, Sonic and a huge list of others. Then you have games that you don't have to play them in order, but playing them in order gives you better insight into the game, such as the Mother Series, KOTOR, Silent Hill, or Phoenix Wright. Then you have games that playing them out of order can lead to someone being completely confused like your example of ME 1 and 2 and also .Dot Hack Sign, Half-Life (mostly after HL2) and others that have a direct story line tie in.
So while skipping ahead in the series isn't a huge deal some of the time, it can be for some very specific series. Sometimes I try to play things in order, if the story calls for it.