Rick's suggestions are a good start. Take your pick.
https://www.ricksteves.com/europe/czech-republic/prague
Rather than a checklist of museums, Prague is a fine place to wander around and just take in the fun atmosphere. Plan some worthwhile activities — take a self-guided tram tour, hire a local guide, enjoy a concert, or go for a scenic paddle on the river.
In the Old Town
▲▲▲ Old Town Square Magical main square of Old World Prague, with dozens of colorful facades, the dramatic Jan Hus Memorial, looming Týn Church, and fanciful Astronomical Clock.
▲▲▲ Charles Bridge An atmospheric, statue-lined bridge that connects the Old Town to the Little Quarter and Prague Castle.
▲▲▲ Jewish Quarter The finest collection of Jewish sights in Europe, featuring various synagogues and an evocative cemetery.
▲▲ Museum of Medieval Art The best Gothic art in the country, at the former Convent of St. Agnes.
▲ Havelská Market Colorful open-air market that sells crafts and produce.
▲ Klementinum National Library's lavish Baroque Hall and Observatory Tower (with views), open by 45-minute tour only.
In the New Town
▲▲ Wenceslas Square Lively boulevard at the heart of modern Prague.
▲▲ Mucha Museum Easy-to-appreciate collection of Art Nouveau works by Czech artist Alfons Mucha.
▲▲ Municipal House Pure Art Nouveau architecture, including Prague's largest concert hall and several eateries.
▲▲ Museum of Communism The rise and fall of the regime, from start to Velvet finish.
▲ National Memorial to the Heroes of the Heydrich Terror Tribute to members of the resistance, who assassinated a notorious Nazi architect of the Holocaust.
▲ Petřín Hill Little Quarter hill with public art, a funicular, and a replica of the Eiffel Tower.
Church of St. Nicholas Jesuit centerpiece of Little Quarter Square, with ultimate High Baroque decor and a climbable bell tower.
Wallenstein Palace Garden Largest and beautiful Renaissance palace garden.
In the Castle Quarter
▲▲▲ St. Vitus Cathedral The Czech Republic's most important church, featuring a climbable tower and a striking stained-glass window by Art Nouveau artist Alfons Mucha.
▲▲ Prague Castle Traditional seat of Czech rulers, with St. Vitus Cathedral, Old Royal Palace, Basilica of St. George, shop-lined Golden Lane, and lots of crowds.
▲▲ Lobkowicz Palace The most entertaining palace in town.
▲ Strahov Monastery and Library Baroque center of learning, with ornate reading rooms and old-fashioned science exhibits.
Beyond the Core
▲▲▲ Alfons Mucha's Slav Epic Twenty enormous canvases at Veletržní Palace depicting momentous events of Slavic history.
▲ Vyšehrad Welcoming, untouristy park at the site of a former hilltop palace, rich with Czech history and great city views.