Great question, especially since so much has come out since this thread was created. I'll make mine a little less childhood this time, though some of those still stand out.
1) UCS Millennium Falcon - Either would deserve to be here. 10179 for how it served as the gold standard for so many years, and 75192 for how much they improved upon it.
2) 10189 Taj Mahal - Amazing set in person. Need to build mine again.
3) 10181 Eiffel Tower - Very impressive in size, honestly needs an update structurally through, similar to 10030
4) 10030 UCS Star Destroyer - I don't own the new one yet, so this will sit in its place for now. Massive but needed the update it got.
5) 42083 Bugatti Chiron - Masterpiece in Technic ingenuity.
6) 10210 Imperial Flagship - Still the gold standard for pirate ships.
7) 6990 Monorail - While not "Classic" space, this is about as coveted a space set as there is and blew everything previous out of the water with the motorized components
8. 71043 Harry Potter Hogwarts Castle - The HP set we wanted for so long in small scale.
9) 10261 Creator Roller Coaster - There are other roller coasters, but the sheer size of this and the ability to motorize it make it a must have for fairground builders
10) 10255 Assembly Square - Using elements of its predecessors, this modular is almost perfect in build techniques, colors, build quality.