Probotector - without a shadow of a doubt. The pick-up-and-play again-and-again readiness that you want from a hand-held game; smooth scrolling (without being so fast it blurred), alternate side-on and overhead levels and all the best features and set-pieces of the
Contra series; and all in a far better sprite:screen size ratio than any
Contra game before or since.
Close runners-up would be
The Legend of Zelda: Link's Awakening (for the most emotionally engaging story of any Zelda adventure before or since),
R-Type (a great conversion, but let down by two missing levels - where were you Bob Pape when we needed you?

) and
Wario Land (Mario but done chunky and fun and with a bit of adventure).
If you only had one for
Tetris then you were missing out - particularly as you could have got a perfectly decent dedicated LCD version of
Tetris for a tenner from Tandy.
Ah, you want a top 5? Last one is tricky. I feel Jon Ritman's
Monster Max should be on there, but it never quite matched up to the fun of
Head over Heels on the Spectrum. So I'll go for
Super R.C. Pro-Am, as another pick-up-and-play game, this time a racer. Into-the screen racing didn't work so well on the GameBoy's little screen; it could go all too fast and just become a blur. So could scrolling (see the disaster that is
Zool), but
Super R.C. Pro-Am, like the other 2D games I've listed, managed to get it just about right.
1.
Probotector
2.
The Legend of Zelda: Link's Awakening
3.
R-Type
4.
Wario Land
5.
Super R.C. Pro-Am