Whisk 2 egg yolks with 1/4 cup sugar until pale. Stir in blood orange juice, zest, and vanilla. Warm gently over low heat while stirring until slightly thickened, then cool.
Beat mascarpone until smooth and fold into cooled yolk mixture. Chill briefly.
Whip cream with powdered sugar to soft peaks. Fold into mascarpone mixture.
Beat 3 egg whites with remaining 1/4 cup sugar to glossy peaks. Fold into mixture gently.
Place sponge layer on a cake plate. If using liqueur, brush cake with it.
Spoon semifreddo over sponge, smooth top, and freeze 2–3 hours until set.
Garnish with thin blood orange slices before serving. Slice with a warm knife.