Tenchi Muyo OVA - Tenchi Muyo set the standard for one of the most popular genres today, the harem anime. The story follows Tenchi, a fairly normal boy until girls from outerspace start showing up. Whether it's the Princess Ayeka or the fiery pirate Ryoko, all of them seem to have a thing for poor Tenchi. Hilarious antics ensue as the group seems to bounce from one possible disaster to another. Anyone who has seen the likes of Love Hina or similar series would be well advised to search this title out.
Grave of the Fireflies - Possibly the most moving movie, animated or not, that I have watched. Set against the backdrop of WW2 Japan, the story follows to young children who have been orphaned by American firebombings of their home town. As they are forgotten by their country and abandoned by their extended family, they are forced to fend for themselves. Keep some tissues handy and do yourself a favor, don't watch this if you don't feel like getting depressed.
Neon Genesis Evangelion - This series set a new bar for animation quality in a series when it came out. While the general plot can be viewed as a mecha anime, the characters take center stage through much of the series, developing a depth that is rarely seen in any other series. It also set many of the now ubiquitous traditions seen in mecha anime today (skin tight suits anyone?)
Visions of Escaflowne - Origanally scheduled to be a much longer series, this 26 episode sprint somehow manages to include a great story with a fast pace that set a new level of achievement when it debuted (and thus has no filler episodes
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Naussica of the Valley of the Wind - Picking a Miyyazaki film to put in here was hard, not because I couldn't think of one but because nearly all of them could be listed. Naussica was chosen because of it's staying power (Naussica was voted fans favorite female character in Japan for something like 10 years running). Combined with a wonderful soundtrack and a fast paced plot, Naussica takes you into a world where humans have been pushed to the margins of the land. Miyazaki's environmental stance is never more prevalant, and his artwork is, as always, breathtaking.
Cowboy Bebop - From the jazzy opening riffs, you know your in for a sweet ride in cowboy bebop. A western set in space, the story follows Spike and the crew of the Bebop as they try to make a living as bounty hunters. Many of the episodes are stand alone, but a larger plot slowly developes as they make their way through the solar system. This series also has, imho, the best soundtrack of any anime. The music is perfectly suited to the action on the screen, and varies from heavy metal to blues. The music alone puts this series high on my list, great animation and story makes it a must see.
Akira - This dark anime set off what I consider the second wave of anime fandom in the US. Before it hit the shores in the US, anime was geared towards children, and was often heavily edited. Akira began the changes in American perception that cartoons are just for kids. This gritty futuristic anime has everything from gang wars to shadowy government agencies. The level of violence is high, so definately not recommended for kids.
Ghost in the Shell: Stand Alone Complex - Shirow can do no wrong. His celebrated Ghost in the SHell series finally gets the anime it deserves (the original movie used all of about 5 pages from the origanal manga of over 200 pages). political intruige mixed with plenty of fast paced action, this series will keep you on the edge of your seat. The animation is also of the highest quality, as is the soundtrack.
Seriel Experiments Lain - This gets a nod from me if for no other reason than it was the breakout series for ABe (character designer). This dark sci-fi series will keep you guessing until the very end. If you don't like confusing anime, stay away from this one, it gives up its secrets slowly and unwillingly. Otherwise, it is an absolute gem.
Azumanga Daioh - Follow the antics of a class of high school girls and their teachers. Cute at times, and side splittingly funny at others, this anime is comprised of a series of shorts as opposed to a larger overall plot.
Honorable Mention:
Record of Lodoss Wars
Marmalade Boy
Nadia: Secret of Blue Water
Please Save My Earth
Juuni Kokuki (Legend of Twelve Kingdoms)
Kare Kano
FLCL
Don't agree with me? Great, post what ten YOU think should make the cut, and why.