This match is more important than the league fixture for Barcelona. They have a considerable lead in a league they have probably already won and the match will be at home. A win will see them in the final of the Copa del Rey. For that reason, one can expect them to field their best line-up.
The trouble for Barcelona is that the thinking on their "best line-up" may have changed after the midweek shock of losing 2-0 to an inferior and far-from-vintage AC Milan side in the Champions League.
Recently, Barcelona have played essentially a striker-less system, with Messi as a false nine, Alexis Sanchez or Pedro (both having disappointing seasons) up front with him, and sometimes Iniesta when Fabregas is started in midfield. Against Milan, a team that were not even particularly defensive, the flaws of this system were on full display. Cesc Fabregas, the inferior player, pushes the superior Iniesta out of his best position. Neither Pedro nor Alexis Sanchez are scoring. Barcelona had no penetration; Messi had a single touch of the ball in the opposition box and Barcelona had only one shot on goal.
There has been reluctance to use Villa this season. He was injured for a time, and upon his return was involved in a public spat with Lionel Messi. Since then he has not featured in an important match and has seen out-of-form players start ahead of him. But he remains the most talented of Barcelona's strikers and he has an invaluable trait: he's willing to shoot from distance. In a team that can struggle when they are not allowed to have the ball in the area (and Madrid are expected, as usual, to play a high line) Villa gives Barcelona the edge. It would be a surprise if he were not to play.
This is an excellent Barcelona team, well on its way to winning a record-breaking season. But any championship winning team has to have luck on its side and this team still has flaws to exploit that Mourinho's men will be well aware of. Some have already been touched on. There are others.
Barcelona continues to be defensively vulnerable. They also rely on Lionel Messi to get them out of scrapes. So far, particularly over the past several weeks, this has worked. They continue to dominate possession, but as Milan's coach put it mid-week "we simply had to ensure that possession was sterile and make use of ours." The breakdown was 35% to 65% possession - but Milan had better chances, more shots on goal and handily won the game.
Barcelona have the second-leg home-advantage, and the away goal after meeting a considerably weakened Madrid in the first leg. They are an excellent team playing at home, but the tie is finely balanced.