The best replacement for prototype is jquery.

The best alternatives to prototype are rated as following:
★★★★★  jquery
★★★★★  infamous
★★★  prototype 2
★★★  pilot
★★  exemplar
★  stereotype
★  infamous which is better
★  just cause 2
★  dojo
★  patent first
★  mootools
★  archetype
★  model
★  singleton
★  prototype
★  proof of concept
★  closure
★  pyrotech
★  assassins creed
★  red faction
  wireframe
  darksiders
  full machine viktor
  yui
  module pattern
  batman arkham asylum
  concept
  leviathan
  __proto__
  red faction guerrilla
  abstract factory
  volume submitter
  extjs
  ghostbusters
  infamous zero punctuation
  non prototype
  sdlc
  crackdown
  jquery rails

Your alternative for prototype is not listed? Suggest!
Speaking about prototype, one probably shouldn't forget about jquery.

Other search terms related to prototype and their ratings are:
★★★★★ jquery
★★ jquery no conflict
★ sdlc
mootools
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Google Trends

Scale is based on the average worldwide traffic of prototype in all years. Click on graph for more.
prototype
jquery
infamous