I am here to tell you that that is simply not true. People call it a niche "serialized" drama, but that's ridiculous, because EVERY SHOW IS SERIALIZED (maybe not The Simpsons. But almost every show). All of them are better when watched in order, and that includes CSI. But how many people actually do that, every time, never missing episodes? Have you never watched a random rerun of a series you don't normally folllow? You did fine, right? I did fine with X-Files.
The point is, your brain will not explode if you watch Lost out of order and/or come late to the party. All those things people talk about, the secret clues and the ZOMG INSANE PLOT TWISTS you have to follow for years? Completely unnecessary. They're bonuses, certainly, and you can make them as complicated as you want to enhance your fun, but they are not required for basic enjoyment purposes. How many people would say it's impossible to understand Grey's Anatomy unless you've seen it from the beginning? Lost is the same way.
At its core, this is still a story about people surviving on an island. Now, they have enhanced that island over the years, stuffing it full of more conspiracy and sci-fi than I'd like, and yes, there are roughly 2,000 characters at one point or another (though they also have a mortality rate of like 50% per season), but there are a limited number of important core characters at any given time. Most of them are quite pretty. The setting certainly is, and even when the stories jump to off-island locations, it's easy to figure out where and why. So tune in, pick a person you like, and hope they don't die while they're off on rescue/hero/salvage/suicide/scouting/war missions. That's really all there is to it.
Oh, also, it's quite relationship-driven, so you can tune in for that element as well.
This message brought to you in honor of the fact that this is your last chance to watch a season in real time from start to finish, and I'd really like the internet to know that it is not the Top-Secret, Exclusive Clique/Cult its fans often purport it to be. I'm not saying you'll love it, I'm just saying not to be intimidated by it.
[Edit: Also, apparently there's a 1-hour recap special before the premiere, which should give you a decent starting platform if you want to jump in tonight.]